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Reprogramming cholesterol metabolism in macrophages and its role in host defense against cholesterol-dependent cytolysins

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Cellular & Molecular Immunology 2022年第3期19卷 327-336页

作者： Min-Sub Lee steven j.Bensinger Department of Molecular and Medical Pharmacology University of CaliforniaLos AngelesCA90095USA Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA90095USA

Cholesterol is a critical lipid for all mammalian cells,ensuring proper membrane integrity,fluidity,and biochemical *** evidence indicates that macrophages rapidly and profoundly reprogram their cholesterol metabolism in response to activation signals to support host defense ***,our understanding of the molecular details underlying how and why cholesterol homeostasis is specifically reshaped during immune responses remains less well *** review discusses our current knowledge of cellular cholesterol homeostatic machinery and introduces emerging concepts regarding how plasma membrane cholesterol is partitioned into distinct *** then discuss how proinflammatory signals can markedly reshape the cholesterol metabolism of macrophages,with a focus on the differences between MyD88-dependent pattern recognition receptors and the interferon signaling *** also discuss recent work investigating the capacity of these proinflammatory signals to selectively reshape plasma membrane cholesterol *** examine how these changes in plasma membrane cholesterol metabolism influence sensitivity to a set of microbial pore-forming toxins known as cholesterol-dependent cytolysins that specifically target cholesterol for their effector *** also discuss whether lipid metabolic reprogramming can be leveraged for therapy to mitigate tissue damage mediated by cholesterol-dependent cytolysins in necrotizing fasciitis and other related *** expect that advancing our understanding of the crosstalk between metabolism and innate immunity will help explain how inflammation underlies metabolic diseases and highlight pathways that could be targeted to normalize metabolic homeostasis in disease states.

关键词： Cholesterol Macrophages Innate Immunity Metabolism

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Autophagy gets in on the regulatory act

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分子细胞生物学报:英文版 2011年第2期3卷 76-77页

作者： steven K.Backues Daniel j.Klionsky Life Sciences Institute University of MichiganAnn ArborMI 48109-2216USA

Autophagy down-regulates the Wnt signal transduction pathway via targeted degradation of a key signaling *** may provide an explanation for autophagy’s role in tumor *** eukaryotic cell has at its disposal two primar... 详细信息

关键词： Autophagy targeted explanation

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An Approximate Riemann Solver for Advection-Diffusion Based on the Generalized Riemann Problem

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Communications on Applied Mathematics and Computation 2020年第3期2卷 515-539页

作者： steven j.ns Claus-Dieter Munz Institute of Aerodynamics and Gas Dynamics University of StuttgartPfafenwaldring 2170569 StuttgartGermany

We construct an approximate Riemann solver for scalar advection-diffusion equations with piecewise polynomial initial *** obj.ctive is to handle advection and diffusion simultaneously to reduce the inherent numerical diffusion produced by the usual advection flux *** approximate solution is based on the weak formulation of the Riemann problem and is solved within a space-time discontinuous Galerkin approach with two *** novel generalized Riemann solver produces piecewise polynomial solutions of the Riemann *** conj.nction with a recovery polynomial,the Riemann solver is then applied to define the numerical flux within a finite volume *** results for a piecewise linear and a piecewise parabolic approximation are *** results indicate a reduction in numerical dissipation compared with the conventional separated flux calculation of advection and ***,it is shown that using the proposed solver only in the vicinity of discontinuities gives way to an accurate and efficient finite volume scheme.

关键词： Generalized Riemann problem Advection-diffusion Discontinuous Galerkin Numerical flux ADER Diffusive generalized Riemann problem Space-time solution Recovery method

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The current trend of autologous costal cartilage harvest by facial plastic surgeons for rhinoplasty in the United States

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Plastic and Aesthetic Research 2019年第2期6卷 1-7页

作者： Clara M.Olcott steven j.Pearlman Inland Ear Nose&Throat-Facial Plastics UplandCA 91784USA Pearlman Aesthetic Surgery New YorkNY 10022USA

Aim: To assess the safety profile and practice trend of autologous costal cartilage harvest by facial plastic surgeons in the United States (US).Methods: A 10-question online survey was distributed by the American Academy of Facial Plastic and Reconstructive Surgery to its ***: Of the 2,639 members, 2,379 received the survey with 137 (5.76%) members responded. The maj.rity (33.6%)of the respondents were expert facial plastic surgeons. One hundred and nine (79.6%) of the respondents performed rib harvest with 49.6% of them performing the procedure at a hospital facility. Among them, 21.5% exclusively performed their surgery at an ambulatory surgical center not physically attached to a hospital while 6.67% of them at the in-office accredited operating room. When comparing techniques, 64.7% performed only full-thickness rib grafts vs. 12.0%harvesting partial-thickness rib grafts. Most used an incision length between 2.1 and 4 cm (64.4%) while 2 surgeons used < 1 cm incision. The occurrence of pneumothorax after autologous rib harvest remained low (< 1%) in most (73.1%).Regarding safety practices of the surgeons, only 24.6% would order a chest X-ray post-operatively while 54.5% would not. In addition, 58.7% of respondents never kept their patients overnight for observation after autologous rib grafting while 15.0% always would. For pain management, most respondents (50.4%) did not utilize any additional analgesia protocol besides oral pain ***: Two thirds of the US facial plastic surgeons performed autologous costal cartilage harvest in a hospital setting. Routine chest imaging or overnight observation post-operatively was not warranted as the percentage of pneumothorax remained low and pain control was adequate.

关键词： Rib graft autologous costal cartilage rhinoplasty current practice pneumothorax

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e-VLBI observations of GRB 080409 afterglow with an Australasian radio telescope network

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Research in Astronomy and Astrophysics 2016年第11期16卷 1-6页

作者： Aquib Moin Philip G. Edwards steven j. Tingay Chris j. Phillips Anastasios K. Tzioumis Shaun W. Amy Tao An Mamoru Sekido Zhong-Xiang Wang Physics Department United Arab Emirates University RO. Box 15551 A1-Ain United Arab Emirates Shanghai Astronomical Observatory Chinese Academy of Sciences Shanghai 200030 China International Centre for Radio Astronomy Research Curtin University Bentley WA Australia CSIRO Astronomy and Space Science P.O. Box 76 Epping NSW 2121 Australia Kashima Space Research Center National Institute of Information and Communications Technology (NICT) 893-1 Hirai Kashima 314-0014 Ibaraki Japan Key Laboratory of Radio Astronomy Chinese Academy of Sciences Nanjing 210008 China Osservatorio di Radio Astronomia Istituto Nazionale di Astrofisica Italy

Transcontinental e-VLBI observations were conducted in j.ne 2008 with telescopes in Australia, China and j.pan. Detections were made of the radio-loud quasar PKS B0727-115, which shows superlu- minal motion, and the intra-day variable quasar PKS B0524＋034. The latter source was used as a phase reference calibrator for observations at the position of the gamma-ray burst GRB 080409, for which an upper limit to the radio emission is set. Australia Telescope Compact Array data were also used to derive a limit on the radio flux density of the GRB afterglow. These observations demonstrate the capability to form a large Australasian radio telescope network for e-VLBI, with data transported and processed in realtime over high capacity networks. This campaign represents the first step towards more regular e-VLBI observations in this region.

关键词： techniques: interferometric -- galaxies: active -- gamma rays: bursts

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Radiofrequency electric-field heating behaviors of highly enriched semiconducting and metallic single-walled carbon nanotubes

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Nano Research 2015年第9期8卷 2859-2870页

作者： Stuart j. Corr Mustafa Raoof Brandon T. Cisneros Alvin W. Orbaek Matthew A. Cheney j.stin j. Law Nadia C. Lara Andrew R. Barron Lon j. Wilsor steven A. Curley Division of Surgery Baylor College of Medicine Houston TX 77030 USA Department of Surgical Oncology University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Department of Chemistry and the Richard E. Smalley Institute for Nanoscale Science and Technology Rice University Houston TX 77005 USA Department of Surgery The University of Arizona College of Medicine Tucson AZ 85724 USA Department of Chemistry and Biochemistry University of California San Diego La Jolla CA 92093 USA College of Engineering Swansea University Singleton Park Swansea SA2 8PP Wales UK Department of Mechanical Engineering and Materials Science Rice University Houston TX 77005 USA

It is theorized that enhanced thermal heating may result from exposing single-walled carbon nanotubes （SWNTs） embedded in a conductive host to radiofrequency （RF） electric fields. We examine the RF-induced （13.56 MHz） heating behaviors of 95% metallic- and semiconducting-enriched SWNTs （m-/s-SWNTs） suspended in aqueous solutions with varying NaC1 molarity （0.001 mM-1 M）. The heating effects were only evident for host molarities below 1 mM （equivalent to 0.1 S/m） at which the s-SWNT heating rates dominated those of the m-SWNTs. The heating effects were localized to aligned and aggregated ＂SWNT ropes＂ -1 cm in length that formed in suspension, parallel to the electric-field vector, during the RF exposure. For molarities above 1 mM, no enhancements were evident, owing to the large heating effects of the bulk ionic NaC1 suspensions, which were observed in previous studies. Although larger enhancement effects proportional to the host conductivity have been theoretically predicted for m-/s-SWNT suspensions, this was not observed most likely because of the aggregation and screening effects, which diminished the scattered electric field near the m-/s-SWNTs. Our research may further the development of better nanoparticle heating agents for applications such as non-invasive RF-induced cancer hyperthermia.

关键词： rad.iofrequency,carbon nanotubes,metallic,semiconducting,hyperthermia

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Patient Characteristics, Safety, and Tolerability With Telaprevir Treatment for HCV in the Clinic:a Retrospective, Multicenter Study

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j.urnal of Clinical and Translational Hepatology 2014年第2期2卷 65-73页

作者： steven L. Flamm Paul j. Pockros Leif Bengtsson Mark Friedman Northwestern University Feinberg School of Medicine Chicago Illinois USA Scripps Clinic and Scripps Translational Science Institute La Jolla California USA Vertex Pharmaceuticals Incorporated Boston Massachusetts USA

Background and Aims: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. Methods: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. Results: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included;62%were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR;32 discontinued due to adverse events. Mean age was 55 years;patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%);35.5%were reported to have cirrhosis at baseline;and 55.3%previously received PR. Hypertension and depres-sion were the most common comorbidities. Patient charac-teristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%;albumin, 5.3%;platelets, 11.5%;and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). Conclusions: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assess-ment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice.

关键词： Hepatitis C virus Combination drug therapy Protease inhibitors Liver diseases

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Portable device to assess dynamic accuracy of global positioning system(GPS)receivers used in agricultural aircraft

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International j.urnal of Agricultural and Biological Engineering 2014年第2期7卷 68-74页

作者： steven j.Thomson Yanbo Huang Lowrey A.Smith United States Department of Agriculture(USDA) Agricultural Research Service(ARS)Crop Production Systems Research UnitStonevilleMS 38776USA

A device was designed to test the dynamic accuracy of Global Positioning System(GPS)receivers used in agricultural aircraft and other aerial *** system works by directing a sun-reflected light beam from the ground to the aircraft using mirrors.A photo detector points downward from the aircraft to detect the light beam,and photo detection circuitry triggers an event in the guidance system data file at the aircraft’s location corresponding to the precisely georeferenced position on the *** details are presented on the mirror-based light reflection system and photo-electronic circuitry designed to trigger an event in the guidance system’s log *** example application evaluated the horizontal accuracy of a stand-alone GPS receiver by matching dynamic data with data from the aircraft’s guidance *** indicated a 2.16 s lead in position registered by the stand-alone receiver over that registered by the aircraft’s guidance system GPS receiver,which had been previously evaluated to be within 0.13 s of Real-Time Kinematic(RTK)-referenced time and position.

关键词： GPS receiver accuracy agricultural aircraft aerial application remote sensing georeferencing UAV

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Stellar interiors 2ed.

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丛书名： Astronomy and astrophysics library

2004年

作者： Carl j. Hansen steven D Kawaler Virginia Trimble

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Mitogen-activated protein kinases mediate the oxidative burst and saponin synthesis induced by chitosan in cell cultures of Panax ginseng

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Science China(Life Sciences) 2004年第4期47卷 303-312页

作者： steven j. NEILL Centre for Research in Plant Science University of the West of England Bristol Coldharbour Lane Bristol BS16 1QY United Kingdom

Chitosan (CHN) specially induced the activities of 39 kD and 42 kD protein kinases in ginseng cells, which could be suppressed by an inhibitor of mitogen-activated protein kinase (MAPK) pathway, PD98059. The immunoprecipitation (IP) using MAPK antibody or kinase assay in vitro also showed that CHN-induced 42 kD and 39 kD protein kinases belonged to the MAPK family. PD98059 suppressed CHN-induced transcriptions of ginseng squalene synthase and ginseng squalene epoxidase genes (gss and gse), CHN-induced accumulation of β-Amyrin synthase (β-AS) and synthesis of saponin. These results showed that CHN-induced activities of MAPKs were necessary for the CHN-induced saponin synthesis. EGTA and LaCl3 suppressed CHN-induced 39 kD and 42 kD MAPK activities. Ruthenium red (RR) could suppress CHN-induced 39 kD activity. All of them suppressed CHN-induced saponin synthesis. These results indicated that CHN-induced increment of cytosolic calcium was necessary for CHN-induced saponin synthesis. PD98059 also suppressed CHN-induced oxidative burst (including the increment of activity of plasma membrane NADPH oxidase and production of H2O2), but diphenylene iodonium (DPI), dimethylthiourea (DMTU) and 2,5-dihydroxycinnamic acid methyl ester (DHC) could not suppress CHN-induced MAPK activities, which indicated that MAPK was possibly function upstream of CHN-induced oxidative burst. Keywords mitogen-activated protein kinase - chitosan - saponin

关键词： mitogen-activated protein kinase,chitosan,saponin.

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