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Macrophage-specific inhibition of the histone demethylase jMjD3 decreases STING and pathologic inflammation in diabetic wound repair

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Cellular & Molecular Immunology 2022年第11期19卷 1251-1262页

作者： Christopher O.Audu William j.Melvin Amrita D.joshi Sonya j.Wolf jadie Y.Moon Frank M.Davis Emily C.Barrett Kevin D.Mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam C.Tsoi Sriganesh B.Sharma tyler M.Bauer james Shadiow Matthew A.Corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany BMoore johann EGudjonsson Andrew MSmith Katherine A.Gallagher Department of Surgery Section of Vascular SurgeryUniversity of MichiganAnn ArborMIUSA Department of Microbiology and Immunology University of MichiganAnn ArborMIUSA Department of Medicinal Chemistry University of MichiganAnn ArborMIUSA Department of Surgery Section of General SurgeryUniversity of MichiganAnn ArborMIUSA Department of Bioengineering University of IllinoisUrbana-ChampaignChampaignILUSA Department of Dermatology University of MichiganAnn ArborMIUSA Department of Pathology University of MichiganAnn ArborMIUSA Department of Surgery University of Texas Southwestern Medical CenterDallasTXUSA

Macrophage plasticity is critical for normal tissue repair following *** pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are ***,using single-cell RNA sequencing of human diabetic wounds,we identified increased jMjD3 in diabetic wound macrophages,resulting in increased inflammatory gene ***,we report that in wound healing,jMjD3 directs early macrophage-mediated inflammation via jAK1,3/STAT3 ***,in the diabetic state,we found that IL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates jMjD3 expression in diabetic wound macrophages via the jAK1,3/STAT3 pathway and that this late increase in jMjD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 ***,RNA sequencing of wound macrophages isolated from mice with jMjD3-deficient myeloid cells(jmjd3f/fLyz2Cre+)identified that the STING gene(Tmem173)is regulated by jMjD3 in wound *** limits inflammatory cytokine production by wound macrophages during ***,in diabetic mice,its role changes to limit wound repair and enhance *** finding is important since STING is associated with chronic inflammation,and we found STING to be elevated in human and murine diabetic wound macrophages at late time ***,we demonstrate that macrophage-specific,nanoparticle inhibition of jMjD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and *** together,this work highlights the central role of jMjD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

关键词： wound healing epigenetics diabetes jMjD3 STING

Intrinsic carrier multiplication in layered Bi_(2)O_(2)Se avalanche photodiodes with gain bandwidth product exceeding 1 GHz

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Nano Research 2021年第6期14卷 1961-1966页

作者： Vinod K.Sangwan joohoon Kang David Lam j.tyler Gish Spencer A.Wells jan Luxa james P.Male Gjeffrey Snyder Zdenek Sofer Mark C.Hersam Department of Materials Science and Engineering Northwestern UniversityEvanstonIL60208USA Department of Inorganic Chemistry University of Chemistry and Technology PragueTechnicka 516628Prague 6Czech Republic Department of Chemistry Northwestern UniversityEvanstonIL60208USA Department of Electrical and Computer Engineering Northwestern UniversityEvanstonIL60208USA

Emerging layered semiconductors present multiple advantages for optoelectronic technologies including high carrier mobilities,strong light-matter interactions,and tunable optical absorption and ***,metal-semiconductor-metal avalanche photodiodes(APDs)are fabricated from Bi2O2Se crystals,which consist of electrostatically bound[Bi2O2]2+and[Se]2−*** resulting APDs possess an intrinsic carrier multiplication factor up to 400 at 7 K with a responsivity gain exceeding 3,000 A/W and bandwidth of~400 kHz at a visible wavelength of 515.6 nm,ultimately resulting in a gain bandwidth product exceeding 1 *** to exceptionally low dark currents,Bi2O2Se APDs also yield high detectivities up to 4.6×1014 jones.A systematic analysis of the photocurrent temperature and bias dependence reveals that the carrier multiplication process in Bi2O2Se APDs is consistent with a reverse biased Schottky diode model with a barrier height of~44 meV,in contrast to the charge trapping extrinsic gain mechanism that dominates most layered semiconductor *** this manner,layered Bi2O2Se APDs provide a unique platform that can be exploited in a diverse range of high-performance photodetector applications.

关键词： layered semiconductor photodetector high-frequency Schottky diode impact ionization

Comparative functional genomics identifies an iron-limited bottleneck in a Saccharomyces cerevisiae strain with a cytosolic-localized isobutanol pathway

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Synthetic and Systems Biotechnology 2022年第2期7卷 738-749页

作者： Francesca V.Gambacorta Ellen R.Wagner tyler B.jacobson Mary Tremaine Laura K.Muehlbauer Mick A.McGee justin j.Baerwald Russell L.Wrobel john F.Wolters Mike Place joshua j.Dietrich Dan Xie jose Serate Shabda Gajbhiye Lisa Liu Maikayeng Vang-Smith joshua j.Coon Yaoping Zhang Audrey P.Gasch Daniel Amador-Noguez Chris Todd Hittinger Trey K.Sato Brian F.Pfleger DOE Great Lakes Bioenergy Research Center University of Wisconsin-MadisonMadisonWIUSA Department of Chemical and Biological Engineering University of Wisconsin-MadisonMadisonWIUSA Laboratory of Genetics Center for Genomic Science InnovationUniversity of Wisconsin-MadisonMadisonWIUSA Department of Bacteriology University of Wisconsin-MadisonMadisonWIUSA Department of Chemistry University of Wisconsin-MadisonMadisonWIUSA Wisconsin Energy Institute J.F.Crow Institute for the Study of EvolutionUniversity of Wisconsin-MadisonMadisonWIUSA Department of Biomolecular Chemistry University of Wisconsin-MadisonMadisonWIUSA

Metabolic engineering strategies have been successfully implemented to improve the production of isobutanol,a next-generation biofuel,in Saccharomyces ***,we explore how two of these strategies,pathway re-localization and redox cofactor-balancing,affect the performance and physiology of isobutanol producing *** equipped yeast with isobutanol cassettes which had either a mitochondrial or cytosolic localized isobutanol pathway and used either a redox-imbalanced(NADPH-dependent)or redox-balanced(NADH-dependent)ketol-acid reductoisomerase *** then conducted transcriptomic,proteomic and metabolomic analyses to elucidate molecular differences between the engineered *** localization had a large effect on isobutanol production with the strain expressing the mitochondrial-localized enzymes producing 3.8-fold more isobutanol than strains expressing the cytosolic ***-balancing did not improve isobutanol titers and instead the strain with the redox-imbalanced pathway produced 1.5-fold more isobutanol than the balanced version,albeit at low overall pathway *** genomic analyses suggested that the poor performances of the cytosolic pathway strains were in part due to a shortage in cytosolic Fe-S clusters,which are required cofactors for the dihydroxyacid dehydratase *** then demonstrated that this cofactor limitation may be partially recovered by disrupting iron homeostasis with a fra2 mutation,thereby increasing cellular iron *** resulting isobutanol titer of the fra2 null strain harboring a cytosolic-localized isobutanol pathway outperformed the strain with the mitochondrial-localized pathway by 1.3-fold,demonstrating that both localizations can support flux to isobutanol.

关键词： Saccharomyces cerevisiae Isobutanol Functional genomics analysis Pathway localization Fe incorporation

Clinical controversies in endoscopic ultrasound

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Gastroenterology Report 2013年第1期1卷 33-41页

作者： Arvind j.Trindade tyler M.Berzin Center for Advanced Endoscopy Division of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA.USA

The field of diagnostic and therapeutic endoscopic ultrasound(EUS)is growing *** EUS has enhanced our ability to diagnose and treat a wide variety of GI conditions,there are many controversial issues regarding the appropriate application of EUS *** this review we discuss five controversial topics in EUS:the utility of EUS in staging of esophageal and gastric cancer;selection of appropriate needle gauge for fine needle aspiration(FNA);use of the stylet in FNA;and the emerging role of contrast agents in endoscopic ultrasound.

关键词： Endoscopic ultrasound controversies gastric cancer esophageal cancer contrast enhanced fine needle aspiration

Discovery of high-entropy ceramics via machine learning

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npj Computational Materials 2020年第1期6卷 1323-1331页

作者： Kevin Kaufmann Daniel Maryanovsky William M.Mellor Chaoyi Zhu Alexander S.Rosengarten tyler j.Harrington Corey Oses Cormac Toher Stefano Curtarolo Kenneth S.Vecchio Department of NanoEngineering UC San DiegoLa JollaCA 92093USA Department of Cognitive Science UC San DiegoLa JollaCA 92093USA Materials Science and Engineering Program UC San DiegoLa JollaCA 92093USA Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Materials Science Electrical EngineeringPhysics and ChemistryDuke UniversityDurhamNC 27708USA

Although high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications,predicting their formation remains a hindrance for rational discovery of new *** approaches are based on physical intuition and/or expensive trial and error *** computational methods rely on the availability of sufficient experimental data and computational *** learning(ML)applied to materials science can accelerate development and reduce *** this study,we propose an ML method,leveraging thermodynamic and compositional attributes of a given material for predicting the synthesizability(i.e.,entropy-forming ability)of disordered metal carbides.

关键词： ceramics entropy attracting

Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

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World journal of Gastroenterology 2016年第29期22卷 6742-6756页

作者： tyler j Severson Siddesh Besur Herbert L Bonkovsky Department of Gastroenterology and Hepatology Wake Forest University NC Baptist Medical Center Abdominal Transplant Program Aurora St Luke’s Medical Center

AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease(NAFLD) onset, severity, and outcome through systematic literature review. METHODS: The authors conducted both systematic and specific searches of Pub Med through December 2015 with special emphasis on more recent data(from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur. RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148 M variant, TM6SF2, particularly the p. E167 K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine. CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.

关键词： Genetic polymorphisms Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis PNPLA3 TM6SF2

Massively Deployable, Low-Cost Airborne Sensor Motes for Atmospheric Characterization

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Wireless Sensor Network 2020年第1期12卷 1-11页

作者： Michael Bolt j. Craig Prather tyler Horton Mark Adams Department of Electrical and Computer Engineering Auburn University Auburn AL USA

A low-cost airborne sensor mote has been designed for deployment en masse to characterize atmospheric conditions. The designed environmental sensing mote, or eMote, was inspired by the natural shape of auto-rotating maple seeds to fall slowly and gather data along its descent. The eMotes measure and transmit temperature, air pressure, relative humidity, and wind speed estimates alongside GPS coordinates and timestamps. Up to 2080 eMotes can be deployed simultaneously with a 1 Hz sampling rate, but the system capacity increases by 2600 eMotes for every second added between samples. All measured and reported data falls within accuracy requirements for reporting with both the World Meteorological Organization (WMO) and the National Oceanic and Atmospheric Administration (NOAA). This paper presents the design and validation of the eMote system alongside discussions on the implementation of a large-scale, low-cost sensor network. The eMote represents unprecedented in-situ atmospheric measurement capabilities with the ability to deploy more than 260 times the number of sensing units as the most comparable commercially available dropsonde.

关键词： Atmospheric Sensing Airborne Biomimetic MF-TDMA

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眼部疾患中视网膜时间反应的精神物理学评价

眼科学报 1986年第2期2卷 109-116页

作者： C.W.tyler W.j.K.Ernst Smith-Kettlewell Institute for Visual Sciences U.S.A. Institute of Ophthalmology London U.K.

用精神物理学方法测量了闪烁光视觉敏感度以表示为时间频率的函数。使用这种方法测试了不同的视网膜病患者,包括青光眼组、几种类型的视网膜色素变性、糖尿病性视网膜病变和尼古丁中毒。结果表明在同一种疾病或同一亚组病人中,中央视网... 详细信息

用精神物理学方法测量了闪烁光视觉敏感度以表示为时间频率的函数。使用这种方法测试了不同的视网膜病患者,包括青光眼组、几种类型的视网膜色素变性、糖尿病性视网膜病变和尼古丁中毒。结果表明在同一种疾病或同一亚组病人中,中央视网膜敏感度实际受损形式是相似的。不同类型的疾病敏感度受损的形式是不同的。本文结果提示,在视网膜对视觉信息的处理中,受试验的视网膜疾病对视网膜的不同部位会有影响。

关键词：视网膜物理学反应

Incremental Investment Value of Wild Turkey Management on the South Carolina Piedmont

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Natural Resources 2014年第12期5卷 719-731页

作者： joseph D. Hammond Thomas j. Straka tyler A. Brown Divison of Natural Resources Clemson University Clemson SC USA National Wild Turkey Federation Edgefield SC USA

Optimal timber production and healthy wild turkey populations can be jointly achieved by balancing cutting cycles, habitat types, and food sources. Expected financial returns from wild turkey management and the habitat required to maintain those returns are estimated. A geographical information system (GIS) is used to illustrate the methodology necessary to distinguish various levels of potential quality turkey habitat, including broad forest conditions across ownerships, like early successional habitat, pine hardwood mixtures, and forest openings, that intermix and combine to form superior wild turkey habitat. A financial analysis framework that considers key financial variables is applied across management regimes to determine net present values, land expectation values, and equivalent annual incomes. Incremental hunting lease revenue from wild turkey hunting leases is shown to impact investment return. The financial framework allows managers to perform sensitivity analyses of costs and revenues to better evaluate management alternatives.

关键词： Wild Turkey Habitat Management Financial Analysis GIS Analysis