Medicine and Health Sciences Commons^™

Advances In Mass Spectrometry On Membrane Proteins, Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L Gross

2020-Current year OA Pubs

Understanding the higher-order structure of membrane proteins (MPs), which are vital for numerous biological processes, is crucial for comprehending their function. Although several biophysical approaches have been used to study the structure of MPs, limitations exist owing to the proteins' dynamic nature and heterogeneity. Mass spectrometry (MS) is emerging as a powerful tool for investigating membrane protein structure and dynamics. Studying MPs using MS, however, must meet several challenges including the lack of stability and solubility of MPs, the complexity of the protein-membrane system, and the difficulty of digestion and detection. To meet these challenges, recent advances in MS have …

Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased …

Serologic Responses To Covid-19 Vaccination In Children With History Of Multisystem Inflammatory Syndrome (Mis-C), Maria A Perez, Carol M Kao, David A Hunstad, Et Al.

2020-Current year OA Pubs

Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n = 16) …

Direct Selection Of Dna-Encoded Libraries For Biased Agonists Of Gpcrs On Live Cells, Bo Cai, Amal El Daibani, Yuntian Bai, Tao Che, Casey J Krusemark

2020-Current year OA Pubs

G protein-coupled receptors (GPCRs) are the largest superfamily of human membrane target proteins for approved drugs. GPCR ligands can have a complex array of pharmacological activities. Among these activities, biased agonists have potential to serve as both chemical probes to understand specific aspects of receptor signaling and therapeutic leads with more specific, desired activity. Challenges exist, however, in the development of new biased activators due, in part, to the low throughput of traditional screening approaches. DNA-encoded chemical libraries (DELs) dramatically improve the throughput of drug discovery by allowing a collective selection, rather than discrete screening, of large compound libraries. The …

Coronavirus Accessory Protein Orf3 Biology And Its Contribution To Viral Behavior And Pathogenesis, Fusheng Si, Shuai Song, Ruisong Yu, Zhen Li, Wenqiang Wei, Chao Wu

2020-Current year OA Pubs

Coronavirus porcine epidemic diarrhea virus (PEDV) is classified in the genus

Loss Of Fgf9 In Mice Leads To Pancreatic Hypoplasia And Asplenia, Sophie Patzek, Zhe Liu, Sean De La O, Sean Chang, Lauren E Byrnes, Xiuqin Zhang, David M Ornitz, Julie B Sneddon

2020-Current year OA Pubs

Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the

Refining Expert Recommendations For Implementing Change (Eric) Strategy Surveys Using Cognitive Interviews With Frontline Providers, Vera Yakovchenko, Matthew J Chinman, Carolyn Lamorte, Byron J Powell, Thomas J Waltz, Monica Merante, Sandra Gibson, Brittney Neely, Timothy R Morgan, Shari S Rogal

2020-Current year OA Pubs

BACKGROUND: The Expert Recommendations for Implementing Change (ERIC) compilation includes 73 defined implementation strategies clustered into nine content areas. This taxonomy has been used to track implementation strategies over time using surveys. This study aimed to improve the ERIC survey using cognitive interviews with non-implementation scientist clinicians.

METHODS: Starting in 2015, we developed and fielded annual ERIC surveys to evaluate liver care in the Veterans Health Administration (VA). We invited providers who had completed at least three surveys to participate in cognitive interviews (October 2020 to October 2021). Before the interviews, participants reviewed the complete 73-item ERIC survey and marked …

Single-Nucleus Rna-Sequencing Of Autosomal Dominant Alzheimer Disease And Risk Variant Carriers, Logan Brase, Shih-Feng You, Ricardo D'Oliveira Albanus, Brenna C Novotny, Carolina Soriano-Tarraga, Taitea Dykstra, Maria Victoria Fernandez, John P Budde, Kristy Bergmann, John C Morris, Randall J Bateman, Richard J Perrin, Eric Mcdade, Chengjie Xiong, Jonathan Kipnis, Celeste M Karch, Oscar Harari, Et Al.

2020-Current year OA Pubs

Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and …

Plasma Proteomics Of Sars-Cov-2 Infection And Severity Reveals Impact On Alzheimer's And Coronary Disease Pathways, Lihua Wang, Daniel Western, Jigyasha Timsina, Charlie Repaci, Joanne Norton, Pat Kohlfeld, John Budde, Omar H Butt, Alan R Templeton, Jane O'Halloran, Rachel Presti, Charles W Goss, Philip A Mudd, Beau M Ances, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Identification of proteins dysregulated by COVID-19 infection is critically important for better understanding of its pathophysiology, building prognostic models, and identifying new targets. Plasma proteomic profiling of 4,301 proteins was performed in two independent datasets and tested for the association for three COVID-19 outcomes (infection, ventilation, and death). We identified 1,449 proteins consistently associated in both datasets with any of these three outcomes. We subsequently created highly accurate models that distinctively predict infection, ventilation, and death. These proteins were enriched in specific biological processes including cytokine signaling, Alzheimer's disease, and coronary artery disease. Mendelian randomization and gene network analyses identified …

Mutational Analysis Of Anesthetic Binding Sites And Their Effects On Gabaa Receptor Activation And Modulation By Positive Allosteric Modulators Of The Α7 Nicotinic Receptor, Spencer R Pierce, Allison L Germann, Sophia Q Xu, Saumith L Menon, Marcelo O Ortells, Hugo R Arias, Gustav Akk

2020-Current year OA Pubs

The positive allosteric modulators (PAMs) of the α7 nicotinic receptor

Cerebral Oximetry Monitoring In Extremely Preterm Infants, Mathias L Hansen, Zachary Vesoulis, Et Al.

2020-Current year OA Pubs

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.

METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis.

RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative …

Reversing Dysdynamism To Interrupt Mitochondrial Degeneration In Amyotrophic Lateral Sclerosis, Gerald W Dorn Ii

2020-Current year OA Pubs

Amyotrophic lateral sclerosis is one of several chronic neurodegenerative conditions in which mitochondrial abnormalities are posited to contribute to disease progression. Therapeutic options targeting mitochondria include enhancing metabolism, suppressing reactive oxygen production and disrupting mitochondria-mediated programmed cell death pathways. Herein is reviewed mechanistic evidence supporting a meaningful pathophysiological role for the constellation of abnormal mitochondrial fusion, fission and transport, collectively designated mitochondrial dysdynamism, in ALS. Following this is a discussion on preclinical studies in ALS mice that seemingly validate the idea that normalizing mitochondrial dynamism can delay ALS by interrupting a vicious cycle of mitochondrial degeneration, leading to neuronal die-back …

A Somato-Cognitive Action Network Alternates With Effector Regions In Motor Cortex, Evan M Gordon, Roselyne J Chauvin, Andrew N Van, Aishwarya Rajesh, Ashley Nielsen, Dillan J Newbold, Nicole A Seider, Samuel R Krimmel, Kristen M Scheidter, Julia Monk, Ryland L Miller, Athanasia Metoki, David F Montez, Annie Zheng, Tomoyuki Nishino, Michael J Myers, Sydney Kaplan, Carolina Badke D'Andrea, Deanna M Barch, Christopher D Smyser, Cynthia E Rogers, Kelly N Botteron, John R Pruett, Jon T Willie, Peter Brunner, Joshua S Shimony, Benjamin P Kay, Scott Marek, Scott A Norris, Chad M Sylvester, Jarod L Roland, Steven E Petersen, Marcus E Raichle, Timothy O Laumann, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations

Mapping Genomic Regulation Of Kidney Disease And Traits Through High-Resolution And Interpretable Eqtls, Seong Kyu Han, Parker C Wilson, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5371 GLOM and 9787 TUBE genes with at least one variant significantly associated with expression (eGene) by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an "integrative prior" for Bayesian statistical fine-mapping. The use of an integrative prior resulted in higher resolution eQTLs illustrated by (1) smaller numbers of …

Head-To-Head Comparison Of 10 Plasma Phospho-Tau Assays In Prodromal Alzheimer's Disease, Shorena Janelidze, Nicolas R Barthélemy, Yingxin He, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status and predict future progression to Alzheimer's dementia. The study included 135 patients with baseline diagnosis of mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average of 4.9 years. Seventy-one participants had abnormal Aβ-status (i.e. abnormal CSF Aβ42/40) at baseline; and 45 of these Aβ-positive participants progressed to Alzheimer's dementia during follow-up. P-tau concentrations were determined in baseline …

Are Cross-Sectional Safety Climate Survey Results In Operating Room Staff Associated With The Surgical Site Infection Rates In Swiss Hospitals?, Yvonne Pfeiffer, Andrew Atkinson, Judith Maag, Michael A. Lane, David Schwappach, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVES: The aim of this study was to investigate the association between surgical site infections (SSIs), a major source of patient harm, and safety and teamwork climate. Prior research has been unclear regarding this relationship.

DESIGN: Based on the Swiss national SSI surveillance and a survey study assessing (a) safety climate and (b) teamwork climate, associations were analysed for three kinds of surgical procedures.

SETTING AND PARTICIPANTS: SSI surveillance data from 20 434 surgeries for hip and knee arthroplasty from 41 hospitals, 8321 for colorectal procedures from 28 hospitals and 4346 caesarean sections from 11 hospitals and survey responses from …

Dendritic Cells And Cryptosporidium: From Recognition To Restriction, Iti Saraav, L David Sibley

2020-Current year OA Pubs

Host immune responses are required for the efficient control of cryptosporidiosis. Immunity against

Exogenous Exposures Shape Genetic Predisposition To Lipids, Alzheimer's, And Coronary Heart Disease In The Mlxipl Gene Locus, Yury Loika, Elena Loiko, Fan Feng, Eric Stallard, Anatoliy I Yashin, Konstantin Arbeev, Allison L Kuipers, Mary F Feitosa, Michael A Province, Alexander M Kulminski

2020-Current year OA Pubs

Associations of single nucleotide polymorphisms (SNPs) of the

Motixafortide And G-Csf To Mobilize Hematopoietic Stem Cells For Autologous Transplantation In Multiple Myeloma: A Randomized Phase 3 Trial, Zachary D Crees, Michael P Rettig, Reyka G Jayasinghe, Keith Stockerl-Goldstein, Feng Gao, Mark A Schroeder, Ravi Vij, John F Dipersio, Et Al.

2020-Current year OA Pubs

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34

Symptom Management Care Pathway Adaptation Process And Specific Adaptation Decisions, Emily Vettese, Allison A King, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions.

METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, …

Structure Of Anhydrotetracycline-Bound Tet(X6) Reveals The Mechanism For Inhibition Of Type 1 Tetracycline Destructases, Hirdesh Kumar, Emily E Williford, Kevin S Blake, Brett Virgin-Downey, Gautam Dantas, Timothy A Wencewicz, Niraj H Tolia

2020-Current year OA Pubs

Inactivation of tetracycline antibiotics by tetracycline destructases (TDases) remains a clinical and agricultural threat. TDases can be classified as type 1 Tet(X)-like TDases and type 2 soil-derived TDases. Type 1 TDases are widely identified in clinical pathogens. A combination therapy of tetracycline and a TDase inhibitor is much needed to rescue the clinical efficacy of tetracyclines. Anhydrotetracycline is a pan-TDase inhibitor that inhibits both type 1 and type 2 TDases. Here, we present structural, biochemical, and phenotypic evidence that anhydrotetracycline binds in a substrate-like orientation and competitively inhibits the type 1 TDase Tet(X6) to rescue tetracycline antibiotic activity as a …

Feasibility Pilot Trial For The Trajectories Of Recovery After Intravenous Propofol Versus Inhaled Volatile Anesthesia (Thrive) Pragmatic Randomised Controlled Trial, Bethany R Tellor Pennington, Douglas A. Colquhoun, Mark D. Neuman, Mary C. Politi, Allison M. Janda, Cathie Spino, Steven Thelen-Perry, Zhenke Wu, Sathish S. Kumar, Stephen H. Gregory, Michael S. Avidan, Sachin Kheterpal, Thrive Research Group

2020-Current year OA Pubs

INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA.

METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age …

Spike-Phase Coupling Patterns Reveal Laminar Identity In Primate Cortex, Zachary W Davis, Nicholas M Dotson, Tom P Franken, Lyle Muller, John H Reynolds

2020-Current year OA Pubs

The cortical column is one of the fundamental computational circuits in the brain. In order to understand the role neurons in different layers of this circuit play in cortical function it is necessary to identify the boundaries that separate the laminar compartments. While histological approaches can reveal ground truth they are not a practical means of identifying cortical layers in vivo. The gold standard for identifying laminar compartments in electrophysiological recordings is current-source density (CSD) analysis. However, laminar CSD analysis requires averaging across reliably evoked responses that target the input layer in cortex, which may be difficult to generate in …

Brain Deficit Patterns Of Metabolic Illnesses Overlap With Those For Major Depressive Disorder: A New Metric Of Brain Metabolic Disease, Kathryn S Hatch, Si Gao, Yizhou Ma, Alessandro Russo, Neda Jahanshad, Paul M Thompson, Bhim M Adhikari, Heather Bruce, Andrew Van Der Vaart, Aristeidis Sotiras, Mark D Kvarta, Thomas E Nichols, Lianne Schmaal, L Elliot Hong, Peter Kochunov

2020-Current year OA Pubs

Metabolic illnesses (MET) are detrimental to brain integrity and are common comorbidities in patients with mental illnesses, including major depressive disorder (MDD). We quantified effects of MET on standard regional brain morphometric measures from 3D brain MRI as well as diffusion MRI in a large sample of UK BioBank participants. The pattern of regional effect sizes of MET in non-psychiatric UKBB subjects was significantly correlated with the spatial profile of regional effects reported by the largest meta-analyses in MDD but not in bipolar disorder, schizophrenia or Alzheimer's disease. We used a regional vulnerability index (RVI) for MET (RVI-MET) to measure …

Simultaneous Inhibition Of Thrombosis And Inflammation Is Beneficial In Treating Acute Myocardial Infarction, Ian Vargas, Ryan P Grabau, Junjie Chen, Carla Weinheimer, Attila Kovacs, William Dominguez-Viqueira, Adam Mitchell, Samuel A Wickline, Hua Pan

2020-Current year OA Pubs

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered …

A Peptide-Centric Quantitative Proteomics Dataset For The Phenotypic Assessment Of Alzheimer's Disease, Gennifer E Merrihew, Randall Bateman, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is a looming public health disaster with limited interventions. Alzheimer's is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain …

A Systematic Review Of Multimodal Brain Age Studies: Uncovering A Divergence Between Model Accuracy And Utility, Robert J Jirsaraie, Aaron J Gorelik, Martins M Gatavins, Denis A Engemann, Ryan Bogdan, Deanna M Barch, Aristeidis Sotiras

2020-Current year OA Pubs

Brain aging is a complex, multifaceted process that can be challenging to model in ways that are accurate and clinically useful. One of the most common approaches has been to apply machine learning to neuroimaging data with the goal of predicting age in a data-driven manner. Building on initial brain age studies that were derived solely from T1-weighted scans (i.e., unimodal), recent studies have incorporated features across multiple imaging modalities (i.e., "multimodal"). In this systematic review, we show that unimodal and multimodal models have distinct advantages. Multimodal models are the most accurate and sensitive to differences in chronic brain disorders. …

Single-Cell Discovery And Multiomic Characterization Of Therapeutic Targets In Multiple Myeloma, Lijun Yao, Julia T Wang, Reyka G Jayasinghe, Julie O'Neal, Chia-Feng Tsai, Michael P Rettig, Yizhe Song, Ruiyang Liu, Yanyan Zhao, Omar M Ibrahim, Mark A Fiala, Julie M Fortier, Siqi Chen, Leah Gehrs, Fernanda Martins Rodrigues, Michael C Wendl, Daniel Kohnen, Andrew Shinkle, Song Cao, Steven M Foltz, Daniel Cui Zhou, Erik Storrs, Matthew A Wyczalkowski, Smrithi Mani, Scott R Goldsmith, Feng Chen, Ravi Vij, Li Ding, John F Dipersio, Et Al.

2020-Current year OA Pubs

UNLABELLED: Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow …

Mek Inhibition Synergizes With Tyk2 Inhibitors In Nf1-Associated Malignant Peripheral Nerve Sheath Tumors, Dana C Borcherding, Neha V Amin, Kevin He, Xiaochun Zhang, Yang Lyu, Carina Dehner, Himanshi Bhatia, Angad Gothra, Layla Daud, Peter Ruminski, Christine A Pratilas, Kai Pollard, Taylor Sundby, Brigitte C Widemann, Angela C Hirbe

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with limited treatment options and poor survival rates. About half of MPNST cases are associated with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Overexpression of TYK2 occurs in the majority of MPNST, implicating TYK2 as a therapeutic target.

EXPERIMENTAL DESIGN: The effects of pharmacologic TYK2 inhibition on MPNST cell proliferation and survival were examined using IncuCyte live cell assays in vitro, and downstream actions were analyzed using RNA-sequencing (RNA-seq), qPCR arrays, and validation of protein changes with the WES automated Western system. Inhibition of TYK2 alone and in combination …

Integrated Model Of The Vertebrate Augmin Complex, Sophie M Travis, Brian P Mahon, Wei Huang, Meisheng Ma, Michael J Rale, Jodi Kraus, Derek J Taylor, Rui Zhang, Sabine Petry

2020-Current year OA Pubs

Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but lack of structure information about augmin has hindered understanding how it promotes branching. In this work, we combine cryo-electron microscopy, protein structural prediction, and visualization of fused bulky tags via negative stain electron microscopy to identify the location and orientation of each subunit within the augmin …