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Cryo-EM structure of the plant 26S proteasome

Plant Communications 2022年第3期3卷 116-126页

作者： Susanne Kandolf Irina Grishkovskaya Katarina Belacic derek l.bolhuis Sascha Amann Brent Foster Richard Imre Karl Mechtler Alexander Schleiffer Hemant D.Tagare Ellen D.Zhong Anton Meinhart Nicholas G.Brown David Haselbach Research Institute of Molecular Pathology(IMP) Vienna BioCenter(VBC)Campus-Vienna-BioCenter 11030 ViennaAustria Department of Radiology and Biomedical Imaging Yale UniversityNew HavenCT 06510USA Department of Pharmacology and lineberger Comprehensive Cancer Center University of North Carolina School of MedicineChapel HillNC 27599USA Computer Science and Artificial Intelligence laboratory Massachusetts Institute of TechnologyCambridgeMA 02139USA Vienna BioCenter PhD Program Doctoral School of the University at Vienna and Medical University of ViennaVienna BioCenter(VBC)ViennaAustria Institute of Physical Chemistry University of FreiburgAlbertstraße 21Freiburg 79104Germany CIBSS Centre for Integrative Biological Signalling Studies University of FreiburgFreiburgGermany

Targeted proteolysis is a hallmark of *** is especially important in long-lived cells that can be found in higher eukaryotes,like *** task is mainly fulfilled by the ubiquitin–proteasome ***,proteolysis by the 26S proteasome is vital to development,immunity,and cell *** the yeast and animal proteasomes are well characterized,there is only limited information on the plant *** determined the first plant 26S proteasome structure from Spinacia oleracea by single-particle electron cryogenic microscopy at an overall resolution of 3.3 A°.We found an almost identical overall architecture of the spinach proteasome compared with the known structures from mammals and ***,we noticed a structural difference in the proteolytic active b1 ***,we uncovered an unseen compression state by characterizing the proteasome’s conformational *** suspect that this new conformation of the 20S core protease,in correlation with a partial opening of the unoccupied gate,may contribute to peptide release after *** data provide a structural basis for the plant proteasome,which is crucial for further studies.

关键词： 26S proteasome spinach UPS cryo-EM conformational landscape

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Seismic behavior assessment for design of integral abutment bridges in Illinois

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Earthquake Engineering and Engineering Vibration 2022年第2期21卷 573-589页

作者： derek l.Kozak larry A.Fahnestock James M.laFave KPFF Consulting Engineers Inc 1601 Fifth AvenueSuite 1600SeattleWA 98101USA Dept.of Civil and Environmental Engineering Univ.of Illinois Urbana-ChampaignUrbanaIL 61801USA

Integral abutment bridges(IABs)minimize deterioration and degradation of the abutment seats and bearings due to water,dirt,and deicing chemicals by eliminating bearings and expansion *** the continuity between superstructure and abutments in an IAB is beneficial for reducing maintenance costs,it leads to more complex behavior under strength and service loading(temperature and traffic)and extreme loading(earthquake).The coupling of superstructure and substructure behavior necessitates system-level analysis of *** seismic IAB studies have typically investigated the behavior of individual IAB components,however a gap of knowledge has developed due to the lack of studies and investigation about the behavior of all IAB components and their interactions with each other in a single analysis *** study uses nonlinear static and dynamic analyses to investigate and assess the seismic behavior of IABs typical to the state of *** analyses aim to bridge the gap of knowledge by evaluating IABs as a whole and utilizing the results to indicate potential vulnerabilities in the design and construction of IABs in Illinois during design-level and larger seismic events,which could not be identified by component-level IAB analyses alone.

关键词： structural analysis seismic design bridge design structural models seismic analysis

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Generalized Baumslag-Solitar Graphs with Soluble Fundamental Groups

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Algebra Colloquium 2014年第1期21卷 53-58页

作者： Alberto l. Delgado derek J.S. Robinson Mathew Timm vDepartment of Mathematics illinois State University Normal IL 61790 USA Department of Mathematics University of Illinois at Urbana-Champaign Urbana IL 61801 USA Department of Mathematics Bradley University Peoria IL 61625 USA

It is shown that the generalized Baumslag-Solitar graphs which have soluble fundamental groups can be constructed from four simple types of graph by a process of decoration. The method of proof is elementary and emplo... 详细信息

关键词： generalized Baumslag-Solitar graph soluble fundamental group

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EFFECT OF COMPOSITION AND PROCESSING CONDITION ON MICROSTRUCTURAl PROPERTIES AND DURABIlITY OF FlUOROPOlYMER/ACRYlIC BlENDS

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Chinese Journal of Polymer Science 2009年第1期27卷 59-69页

作者： derek l.Ho Forrest.A.landis Diep Nguyen National Institute of Standards and Technology (NIST) GaithersburgMDUSA Pennsylvania State University YorkPAUSA Illinois Institute of Technology ChicagoILUSA

Fluoropolymer blends have been widely used as binders for exterior coatings because of their excellent resistance to ultra-violet (UV) radiation as well as to many corrosive chemical *** is known that the fluorinated component usually has a lower glass transition temperature and easily crystallizes in the final structure depending upon the blend composition and sample annealing *** investigated the effect of blend composition and annealing process (slow and fast cooling) on the surface morpho...

关键词： AFM Confocal microscopy Crystallinity Surface morphology Small angle scattering UV exposure

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A historical review of the development of verification and validation theories for simulation models

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International Journal of Modeling, Simulation, and Scientific Computing 2017年第2期8卷 1-24页

作者： Phillip J.Durst derek T.Anderson Cindy l.Bethel U.S.Army Engineer Research and Development Center 3909 Halls Ferry Road Vicksburg MS 39180USA Mississippi State University Department of Electrical and Computer Engineering Mississippi StateMS 39759USA Mississippi State University Department of Computer Science and Engineering Mississippi StateMS 39759USA

Modeling and simulation(M&S)play a critical role in both engineering and basic research ***-based models have existed since the 1950s,and those early models have given way to the more complex computational and physics-based simula-tions used *** such,a great deal of research has been done to establish what level of trust should be given to simulation outputs and how to verify and validate the mod-els used in these *** paper presents an overview of the theoretical work done to date defining formal definitions for,and methods of,verification and validation(V&V)of computer *** models are broken down into three broad cate-gories:analytical and simulation models,computational and physics-based models,and simulations of autonomous systems,and the unique theories and methods developed to address V&V of these models are *** paper also presents the current prob-lems in the theoretical field of V&V for models as simulations move from single system models and simulations to more complex simulation *** particular,this paper high-lights the lack of agreed-upon methods for V&V of simulations of autonomous systems,such as an autonomous unmanned vehicles,and proposes some next steps needed to address this problem.

关键词： Verification and validation simulation models computational models physics-based simulations autonomous systems.

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Hepatocellular carcinoma in non-alcoholic fatty liver disease-a review of an emerging challenge facing clinicians

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Hepatobiliary Surgery and Nutrition 2021年第1期10卷 59-75页

作者： Daniel Geh derek M.Manas Helen l.Reeves Northern Institute for Cancer Research Institute of Cellular Medicine Newcastle UniversityNewcastle upon TyneUK Hepatopancreatobiliary Multidisciplinary Team Newcastle upon Tyne Hospitals NHS Foundation TrustNewcastle upon TyneUK

Importance:Non-alcoholic fatty liver disease(NAFlD)is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma(HCC)in many developed *** presents major challenges for the surveillance,diagnosis and treatment of ***:To discuss the clinical challenges faced by clinicians in managing the rising number of NAFlD-HCC *** Review:MEDlINE,PubMed and Embase databases were searched using the keywords;NAFlD,HCC,surveillance,hepatectomy,liver transplantation,percutaneous ablation,transarterial chemoembolization(TACE),selective internal radiotherapy treatment(SIRT)and *** clinical studies were ***:Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis,whereas in NAFlD a significant proportion of HCC develops in the absence of *** NAFlD patients often present with a more advanced stage of HCC,with a poorer ***-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other *** limits the use of curative treatments such as liver resection and orthotopic liver transplantation(OlT).Evidence suggests that although NAFlD-HCC patients who undergo liver resection or OlT have worse perioperative and short-term outcomes,overall long-term survival is comparable to HCC of other *** highlights the importance of careful patient selection,pre-habilitation and perioperative planning for NAFlD-HCC patients being considered for surgical *** consideration is also important for non-surgical treatments,although the evidence supporting treatment selection is frequently lacking,as these patients tend to be poorly represented in clinical *** therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFlD patients with obesity or *** tyrosine kinase inhibitor sorafenib may also b

关键词： Non-alcoholic fatty liver disease(NAFlD) hepatocellular carcinoma(HCC) liver transplantation hepatectomy catheter ablation sorafenib population surveillance

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IDO1 in cancer: a Gemini of immune checkpoints

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Cellular & Molecular Immunology 2018年第5期15卷 447-457页

作者： lijie Zhai Erik ladomersky Alicia lenzen Brenda Nguyen Ricky Patel Kristen l lauing Meijing Wu derek A Wainwright Department of Neurological Surgery Northwestern University Department of Pediatrics Northwestern University Division of Hematology Oncology and Stem Cell TransplantationNorthwestern University Ann&Robert H.lurie Children’s Hospital of Chicago Northwestern University Department of Medicine-Hematology/Oncology Northwestern University Department of Microbiology-Immunology Northwestern University Department of MedicineDivision of Hematology and Oncology Northwestern UniversityBrain Tumor InstituteNorthwestern University Robert H.lurie Comprehensive Cancer Center of Northwestern University Northwestern UniversityChicagoIL 60611USA

Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as ***,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human *** studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject *** the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously *** to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive *** gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer ***,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。

关键词： glioblastoma glioma IDO immunosuppression kynurenine immunotherapy melanoma Treg

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Diagnosis and surgical management of breast cancer metastatic to the spine

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World Journal of Clinical Oncology 2014年第3期5卷 263-271页

作者： derek G Ju Alp Yurter Ziya l Gokaslan Daniel M Sciubba Department of Neurosurgery The Johns Hopkins Medical InstitutionsJohns Hopkins University

Breast cancer is the most common malignancy and the second leading cause of death in Western women. Breast cancer most commonly metastasizes to the bone and has a particular affinity with the spine, accounting for 2/3 of osseous metastases discovered. With significant improvements in cancer therapies, the number of patients at risk for symptomatic spinal metastases is likely to increase. Patients may suffer from intractable pain and neurological dysfunction, negatively influencing their quality of life. Timely diagnosis of patients is crucial and has been aided by several breakthrough advances in imaging techniques which aid in detection, staging, and follow-up of bone metastases. Breast metastases are usually responsive to hormonal therapy and pharmacologic interventions, but skeletal metastases often require surgical intervention. The treatments are palliative but goals include the preserving or restoring neurologic function, ensuring spinal stability, and relieving pain. Advances in surgical techniques and instrumentation have allowed more effective decompres-sion and stabilization of the spine, and with the support of recent evidence the trend has shifted towards using more advanced surgical options in appropriately selected patients. In this review, the clinical presentation, diagnosis, patient selection, and surgical management of breast cancer metastatic to the spine are discussed.

关键词： Breast cancer Spine Metastasis Surgery Outcomes Decompression

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MEK inhibition activates STAT signaling to increase breast cancer immunogenicity via MHC-I expression

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Cancer Drug Resistance 2020年第3期3卷 603-612页

作者： derek A.Franklin Jamaal l.James Margaret l.Axelrod Justin M.Balko Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37232USA. Department of Pathology Microbiologyand ImmunologyVanderbilt University Medical CenterNashvilleTN 37232USA. Breast Cancer Research Program Vanderbilt University Medical CenterNashvilleTN 37232USA.

Aim:Immunotherapy and immune checkpoint inhibitors(ICI)have changed cancer care for many patients;however,breast cancers have exhibited minimal response to single agent ICI *** is a significant need to identify novel targets capable of increasing cancer cell immunogenicity and response to ICIs in breast *** activated protein kinase(MAPK)signaling is essential for many cellular processes but the relationship between MAPK signaling and cancer cell immunogenicity is less well *** reports suggest that MEK inhibition(MEKi)affects the tumor-immune microenvironment by altering the expression of interferon responsive PD-l1 and MHC-I through unknown ***:Using western blotting and flow cytometry,we sought to determine whether MEKi affects JAK-STAT signaling upstream of PD-l1 and MHC-I expression in a panel of mouse mammary cancer and triple negative breast cancer cell ***:The cell lines tested exhibited increased STAT activation in response to MEKi ***,MEKi-induced MHC-I and PD-l1 expression are dependent upon STAT1 in MMTV-Neu ***,MEKiinduced STAT activation and interferon-responsive protein expression are abrogated with ErbB-family inhibitor co-treatment in MMTV-Neu cells,suggesting ErbB receptor signaling dependence,but not in basal-like cell ***,analysis of basal-like breast cancer patient samples exhibited an inverse relationship between STAT1 and Ras/MAPK activation ***:These findings suggest that MAPK signaling and STAT activation are inversely related in both mouse and human mammary *** work also supports further study of MEKi to increase STAT signaling and potentially,immunotherapy responses through increased MHC-I and PD-l1 expression.

关键词： Mitogen activated protein kinase signaling immunogenicity MHC-I PD-l1

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Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral Science 2013年第3期5卷 130-140页

作者： Carol l Fischer Katherine S Walters David R Drake Deborah V Dawson derek R Blanchette Kim A Brogden Philip W Wertz Dows Institute for Dental Research College of Dentistry The University of Iowa Central Microscopy Research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric Dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

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