Medicine and Health Sciences Commons^™

Resting-State Functional Connectivity Identifies Individuals And Predicts Age In 8-To-26-Month-Olds, Omid Kardan, Sydney Kaplan, Muriah D. Wheelock, Dominique Meyer, Adam T. Eggebrecht, Christopher D. Smyser, Et Al.

2020-Current year OA Pubs

Resting-state functional connectivity (rsFC) measured with fMRI has been used to characterize functional brain maturation in typically and atypically developing children and adults. However, its reliability and utility for predicting development in infants and toddlers is less well understood. Here, we use fMRI data from the Baby Connectome Project study to measure the reliability and uniqueness of rsFC in infants and toddlers and predict age in this sample (8-to-26 months old; n = 170). We observed medium reliability for within-session infant rsFC in our sample, and found that individual infant and toddler's connectomes were sufficiently distinct for successful functional connectome …

Detection Of Brain Tau Pathology In Down Syndrome Using Plasma Biomarkers, Shorena Janelidze, Bradley T Christian, Julie Price, Charles Laymon, Nicole Schupf, William E Klunk, Ira Lott, Wayne Silverman, H Diana Rosas, Shahid Zaman, Mark Mapstone, Florence Lai, Beau M Ances, Benjamin L Handen, Oskar Hansson

2020-Current year OA Pubs

IMPORTANCE: Novel plasma biomarkers, especially phosphorylated tau (p-tau), can detect brain tau aggregates in Alzheimer disease.

OBJECTIVE: To determine which plasma biomarker combinations can accurately detect tau pathological brain changes in Down syndrome (DS).

DESIGN, SETTING, AND PARTICIPANTS: The cross-sectional, multicenter Alzheimer's Biomarker Consortium-Down Syndrome study included adults with DS and a control group of siblings without DS. All participants with plasma, positron emission tomography (PET), and cognitive measures available by the time of data freeze 1.0 were included. Participants were enrolled between 2016 and 2019, and data were analyzed from August 2021 to April 2022.

EXPOSURES: Plasma p-tau217, glial …

Cardiovascular Complications Of Pregnancy-Associated Covid-19 Infections, Joan E Briller, Niti R Aggarwal, Melinda B Davis, Afshan B Hameed, Isabelle Malhamé, Zainab Mahmoud, Emily G Mcdonald, Glaucia Moraes De Oliveira, Odayme Quesada, Nandita S Scott, Jyoti Sharma, American College Of Cardiology Cardiovascular Disease In Women Committee

2020-Current year OA Pubs

Cardiovascular complications are frequently present in coronavirus-2019 (COVID-19) infection. These include microvascular and macrovascular thrombotic complications such as arterial and venous thromboembolism, myocardial injury or inflammation resulting in infarction, heart failure, and arrhythmias. Data suggest increased risk of adverse outcomes in pregnant compared with nonpregnant women of reproductive age with COVID-19 infection, including need for intensive care unit admission, mechanical ventilation, and extracorporeal membrane oxygenation utilization. Current statements addressing COVID-19-associated cardiac complications do not include pregnancy complications that may mimic COVID-19 complications such as peripartum cardiomyopathy, spontaneous coronary artery dissection, and preeclampsia. Unique to pregnancy, COVID-19 complications can result in …

Quantifying Inequities In Covid-19 Vaccine Distribution Over Time By Social Vulnerability, Race And Ethnicity, And Location: A Population-Level Analysis In St. Louis And Kansas City, Missouri, Aaloke Mody, Cory Bradley, Salil Redkar, Branson Fox, Ingrid Eshun-Wilson, Matifadza G. Hlatshwayo, Anne Trolard, Khai Hoan Tram, Lindsey M. Filiatreau, Franda Thomas, Matt Haslam, George Turabelidze, Vetta Sanders-Thompson, William G. Powderly, Elvin H. Geng

2020-Current year OA Pubs

BACKGROUND: Equity in vaccination coverage is a cornerstone for a successful public health response to COVID-19. To deepen understanding of the extent to which vaccination coverage compares with initial strategies for equitable vaccination, we explore primary vaccine series and booster rollout over time and by race/ethnicity, social vulnerability, and geography.

METHODS AND FINDINGS: We analyzed data from the Missouri Department of Health and Senior Services on all COVID-19 vaccinations administered across 7 counties in the St. Louis region and 4 counties in the Kansas City region. We compared rates of receiving the primary COVID-19 vaccine series and boosters relative to …

Snmmi/Acr/Asnc/Scmr Joint Credentialing Statement For Cardiac Pet/Mri: Endorsed By The American Heart Association, Terrence D Ruddy, Mouaz Al-Mallah, James A Arrighi, John P Bois, David A Bluemke, Marcelo F Di Carli, Vasken Dilsizian, Robert J Gropler, Hossein Jadvar, Saurabh Malhotra, Matthier Pelletier-Galarneau, Thomas H Schindler, Pamela K Woodard, Panithaya Chareonthaitawee

2020-Current year OA Pubs

No abstract provided.

Bleeding And Thrombotic Complications Associated With Anticoagulation Prior To Lung Transplantation: A Case Series, Hailey M. Shepherd, Ramsey R. Hachem, Chad A. Witt, Rodrigo V. Guillamet, Derek E. Byers, Benjamin D. Kozower, Bryan F. Meyers, Tsuyoshi Takahashi, G. Alexander Patterson, Varun Puri, Daniel Kreisel, Ruben G. Nava

2020-Current year OA Pubs

Background: Scarce data is available on therapeutic anticoagulation (AC) in patients undergoing pulmonary transplantation. We describe our institutional experience with AC-induced coagulopathy in recipients at the time of transplantation and evaluate its impact on posttransplant outcomes.

Methods: Records of adult patients on therapeutic AC at the time of lung transplantation from January 2014 to July 2021 were reviewed. Administration of preoperative pharmacologic reversal was assessed, with adequate reversal defined as international normalized ratio (INR) ≤1.5. We evaluated the incidence of major bleeding complications [delayed sternal closure, reoperation due to bleeding, chest tube output ≥1,500 cc, ≥4 units of packed red …

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Brian A Van Tine, Et Al

2020-Current year OA Pubs

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression For Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series, Momodou L Jammeh, Alexander Yang, Ahmmad A Abuirqeba, J Westley Ohman, Robert W Thompson

2020-Current year OA Pubs

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge.

OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS.

METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively.

RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 …

Ligand-Based Design, Synthesis, Computational Insights, And In Vitro Studies Of Novel N-(5-Nitrothiazol-2-Yl)-Carboxamido Derivatives As Potent Inhibitors Of Sars-Cov-2 Main Protease, Mohamed Elagawany, Ayman Abo Elmaaty, Ahmed Mostafa, Noura M Abo Shama, Eman Y Santali, Bahaa Elgendy, Ahmed A Al-Karmalawy

2020-Current year OA Pubs

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of

3d Media Stabilizes Membrane And Prolongs Lifespan Of Defolliculated Xenopus Laevis Oocytes, Nikhil D Aggarwal, Steven L Zeng, Ryan J Lashgari, Leland C Sudlow, Mikhail Y Berezin

2020-Current year OA Pubs

No abstract provided.

Non-Targeted Metabolomics Of Cooked Cowpea (Vigna Unguiculata) And Pigeon Pea (Cajanus Cajan) From Ghana Using Two Distinct And Complementary Analytical Platforms, Brooke Sayre-Chavez, Bridget Baxter, Corey D Broeckling, María Muñoz-Amatriaín, Mark Manary, Elizabeth P Ryan

2020-Current year OA Pubs

Legumes are global staple foods with multiple human health properties that merit detailed composition analysis in cooked forms. This study analyzed cowpea [

Mirna Expression Is Increased In Serum From Patients With Semantic Variant Primary Progressive Aphasia, Maria Serpente, Laura Ghezzi, Chiara Fenoglio, Francesca R Buccellato, Giorgio G Fumagalli, Emanuela Rotondo, Marina Arcaro, Andrea Arighi, Daniela Galimberti

2020-Current year OA Pubs

Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 …

Orbitofrontal Cortex Contributes To The Comparison Of Values Underlying Economic Choices, Sébastien Ballesta, Weikang Shi, Camillo Padoa-Schioppa

2020-Current year OA Pubs

Economic choices between goods entail the computation and comparison of subjective values. Previous studies examined neuronal activity in the orbitofrontal cortex (OFC) of monkeys choosing between different types of juices. Three groups of neurons were identified: offer value cells encoding the value of individual offers, chosen juice cells encoding the identity of the chosen juice, and chosen value cells encoding the value of the chosen offer. The encoded variables capture both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that values are compared within OFC. Recent work demonstrates that choices are causally …

[ 18 F]-Labeled Parp-1 Pet Imaging Of Psma Targeted Alpha Particle Radiotherapy Response, Hanwen Zhang, Diane Abou, Peng Lu, Abbie Meghan Hasson, Alexandria Villmer, Nadia Benabdallah, Wen Jiang, David Ulmert, Sean Carlin, Buck E Rogers, Norman F Turtle, Michael R Mcdevitt, Brian Baumann, Brian W Simons, Farrokh Dehdashti, Dong Zhou, Daniel L J Thorek

2020-Current year OA Pubs

The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways-such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [

The University Of Pennsylvania Glioblastoma (Upenn-Gbm) Cohort: Advanced Mri, Clinical, Genomics, & Radiomics, Spyridon Bakas, Aristeidis Sotiras, Sung Min Ha, Et Al

2020-Current year OA Pubs

Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the "University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics" (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer's Disease, Jaclyn M Eissman, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Predicting Which Genes Will Respond To Transcription Factor Perturbations, Yiming Kang, Wooseok J Jung, Michael R Brent

2020-Current year OA Pubs

The ability to predict which genes will respond to the perturbation of a transcription factor serves as a benchmark for our systems-level understanding of transcriptional regulatory networks. In previous work, machine learning models have been trained to predict static gene expression levels in a biological sample by using data from the same or similar samples, including data on their transcription factor binding locations, histone marks, or DNA sequence. We report on a different challenge-training machine learning models to predict which genes will respond to the perturbation of a transcription factor without using any data from the perturbed cells. We find …

Overall Survival With Brentuximab Vedotin In Stage Iii Or Iv Hodgkin's Lymphoma, Stephen M Ansell, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has …

Slc12a8 In The Lateral Hypothalamus Maintains Energy Metabolism And Skeletal Muscle Functions During Aging, Naoki Ito, Ai Takatsu, Hiromi Ito, Yuka Koike, Kiyoshi Yoshioka, Yasutomi Kamei, Shin-Ichiro Imai

2020-Current year OA Pubs

Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and β2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-β2-adrenergic receptor axis. LH-specific overexpression …

Activation Of Nano-Photosensitizers By Y-90 Microspheres To Enhance Oxidative Stress And Cell Death In Hepatocellular Carcinoma, Christopher D Malone, Christopher Egbulefu, Alexander Zheleznyak, Jahnavi Polina, Partha Karmakar, Kvar Black, Monica Shokeen, Samuel Achilefu

2020-Current year OA Pubs

While radioembolization with yttrium-90 (Y-90) microspheres is a promising treatment for hepatocellular carcinoma (HCC), lower responses in advanced and high-grade tumors present an urgent need to augment its tumoricidal efficacy. The purpose of this study was to determine whether clinically used Y-90 microspheres activate light-responsive nano-photosensitizers to enhance hepatocellular carcinoma (HCC) cell oxidative stress and cytotoxicity over Y-90 alone in vitro. Singlet oxygen and hydroxyl radical production was enhanced when Y-90 microspheres were in the presence of several nano-photosensitizers compared to either alone in cell-free conditions. Both the SNU-387 and HepG2 human HCC cells demonstrated significantly lower viability when treated …

Efficient Genome Editing Achieved Via Plug-And-Play Adenovirus Piggyback Transport Of Cas9/Grna Complex On Viral Capsid Surface, Zhi Hong Lu, Jie Li, Igor P Dmitriev, Elena A Kashentseva, David T Curiel

2020-Current year OA Pubs

The capacity to efficiently deliver the gene-editing enzyme complex to target cells is favored over other forms of gene delivery as it offers one-time hit-and-run gene editing, thus improving precision and safety and reducing potential immunogenicity against edited cells in clinical applications. Here we performed a proof-of-mechanism study and demonstrated that a simian adenoviral vector for DNA delivery can be repurposed as a robust intracellular delivery platform for a functional Cas9/guide RNA (gRNA) complex to recipient cells. In this system, the clinically relevant adenovirus was genetically engineered with a plug-and-display technology based on SpyTag003/SpyCatcher003 coupling chemistry. Under physiological conditions, an …

Cryo-Em Structures Of Alphavirus Conformational Intermediates In Low Ph-Triggered Prefusion States, Chun-Liang Chen, Thomas Klose, Chengqun Sun, Arthur S Kim, Geeta Buda, Michael G Rossmann, Michael S Diamond, William B Klimstra, Richard J Kuhn

2020-Current year OA Pubs

Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoproteins rearrange in this process remain unknown. Here, we investigate prefusion cryoelectron microscopy (cryo-EM) structures of eastern equine encephalitis virus (EEEV) under acidic conditions. With models fitted into the low-pH cryo-EM maps, we suggest that E2 dissociates from E1, accompanied by a rotation (∼60°) of the E2-B domain (E2-B) to expose …

Hima2: High-Dimensional Mediation Analysis And Its Application In Epigenome-Wide Dna Methylation Data, Chamila Perera, Haixiang Zhang, Yinan Zheng, Lifang Hou, Annie Qu, Cheng Zheng, Ke Xie, Lei Liu

2020-Current year OA Pubs

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150-3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849-911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, …

Adapting And Developing An Academic And Community Practice Collaborative Care Model For Metastatic Breast Cancer Care (Project Adapt): Protocol For An Implementation Science-Based Study, Ashley J Housten, Uzoma Charles Okere, Graham A Colditz, Cynthia Ma, Jingxia Liu, Courtney Harriss, Nancy U Lin, Melissa Rooney, Jennifer Dill, Muhammad Popalzai, Jennifer Badiu, Kan Huang, Casey Burton, Lindsay Peterson

2020-Current year OA Pubs

BACKGROUND: Metastatic breast cancer (MBC) remains incurable despite significant treatment advances. Coordinating care for patients with MBC can be challenging given the various treatment options, available clinical trials, and frequent need for ancillary services. To optimize MBC care, we designed a project for adapting and developing an academic and community practice collaborative care model for MBC care (Project ADAPT), based on the Ending Metastatic Breast Cancer for Everyone (EMBRACE) program developed at Dana Farber Cancer Institute.

OBJECTIVE: We aim to describe the implementation science-based study design and innovative components of Project ADAPT.

METHODS: Project ADAPT uses the Dynamic Adaptation Process …

Hippocampal Threat Reactivity Interacts With Physiological Arousal To Predict Ptsd Symptoms, Büşra Tanriverdi, Stacey L House, Deanna M. Barch, Et Al.

2020-Current year OA Pubs

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected …

Kstar: An Algorithm To Predict Patient-Specific Kinase Activities From Phosphoproteomic Data, Sam Crowl, Ben T Jordan, Hamza Ahmed, Cynthia X Ma, Kristen M Naegle

2020-Current year OA Pubs

Kinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for …

Oilcloth Sessions As An Implementation Strategy: A Qualitative Study In Denmark, Jeanette Wassar Kirk, Nina Þórný Stefánsdóttir, Byron J Powell, Mette Bendtz Lindstroem, Ove Andersen, Tine Tjørnhøj-Thomsen, Per Nilsen

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to explore healthcare professionals, managers, and other key employees' experiences of oilcloth sessions as a strategy when implementing new emergency departments in Denmark, based on their participations in these sessions. The study addresses the importance of securing alignment in implementation strategies. Too often, this does not get enough attention in the literature and in practice. In this study, alignment among components was achieved in an educational implementation strategy called oilcloth sessions.

METHODS: The study is based on participants' observations of 13 oilcloth sessions and follow-up via 53 semi-structured interviews with the board of …

Myt1l In The Making: Emerging Insights On Functions Of A Neurodevelopmental Disorder Gene, Jiayang Chen, Allen Yen, Colin P Florian, Joseph D Dougherty

2020-Current year OA Pubs

Large scale human genetic studies have shown that loss of function (LoF) mutations in MYT1L are implicated in neurodevelopmental disorders (NDDs). Here, we provide an overview of the growing number of published MYT1L patient cases, and summarize prior studies in cells, zebrafish, and mice, both to understand MYT1L's molecular and cellular role during brain development and consider how its dysfunction can lead to NDDs. We integrate the conclusions from these studies and highlight conflicting findings to reassess the current model of the role of MYT1L as a transcriptional activator and/or repressor based on the biological context. Finally, we highlight additional …

Post-Covid-19 Conditions Among Children 90 Days After Sars-Cov-2 Infection, Anna L. Funk, Fahd D. Ahmad, Et Al.

2020-Current year OA Pubs

No abstract provided.

Electro-Mechanical Coupling Of Kcnq Channels Is A Target Of Epilepsy-Associated Mutations And Retigabine, Nien-Du Yang, Richard Kanyo, Lu Zhao, Jingru Li, Po Wei Kang, Alex Kelly Dou, Kelli Mcfarland White, Jingyi Shi, Jeanne M Nerbonne, Harley T Kurata, Jianmin Cui

2020-Current year OA Pubs

KCNQ2 and KCNQ3 form the M-channels that are important in regulating neuronal excitability. Inherited mutations that alter voltage-dependent gating of M-channels are associated with neonatal epilepsy. In the homolog KCNQ1 channel, two steps of voltage sensor activation lead to two functionally distinct open states, the intermediate-open (IO) and activated-open (AO), which define the gating, physiological, and pharmacological properties of KCNQ1. However, whether the M-channel shares the same mechanism is unclear. Here, we show that KCNQ2 and KCNQ3 feature only a single conductive AO state but with a conserved mechanism for the electro-mechanical (E-M) coupling between voltage sensor activation and pore …