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RANkL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae kibyeong kim keunsoo kang Haemin kim Minjoon Lee brian Oh kaichi kaneko Sungkook Ma Jae Hoon Choi Hojoong kwak Eun Young Lee Sung Ho Park kyung-Hyun Park-Min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA Department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA Department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea Department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea Department of Microbiology Dankook UniversityCheonan3116Republic of Korea Department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANkL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANkL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANkL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANkL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANkL-responsive SEs. The depletion of BATF1/3 inhibited RANkL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANkL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANkL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

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Advances in endovascular aneurysm management: flow modulation techniques with braided mesh devices

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Stroke & Vascular Neurology 2020年第1期5卷 1-13页

作者： Jessica k Campos Barry Cheaney II brian V Lien David A Zarrin Chau D Vo Geoffrey P Colby Li-Mei Lin Alexander L Coon Department of Neurosurgery University of California Irvine School of MedicineOrangeCaliforniaUSA Oregon Health and Science University School of Medicine PortlandOregonUSA Neurosurgery Johns Hopkins UniversityBaltimoreMarylandUSA Johns Hopkins University School of Medicine BaltimoreMarylandUSA UCLA Neurosurgery Ronald Reagan UCLA Medical CenterLos AngelesCaliforniaUSA Carondelet Neurological Institute St.Joseph's HospitalCarondelet Health NetworkTucsonArizonaUnited States

Flow diverters and flow disruption technology,alongside nuanced endovascular techniques,have ushered in a new era of treating cerebral ***,we provide an overview of the latest flow modulation devices and highlight the... 详细信息

关键词： flow braided hered

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Postoperative mometasone irrigations improve quality of life in skull base tumor patients

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 314-319页

作者： Mandy k.Salmon Rijul S.kshirsagar Jacob G.Eide Auddie M.Sweis kathleen Davin Aman Prasad Heather Ungerer Elizabeth Stevens kevin Ig‐Izevbekhai Siddhant Tripathi Tran B.Locke Theodore Lin brian M.Sweis Michael A.kohanski Nithin D.Adappa James N.Palmer Department of Otorhinolaryngology—Headand Neck Surgery University of PennsylvaniaPhiladelphiaPennsylvaniaUSA Division of Otolaryngology—Head and Neck Surgery North Shore University Health SystemThe University of ChicagoEvanstonIllinoisUSA University of Cincinnati School of Medicine CincinnatiOhioUSA Department of Otolaryngology Baylor College of MedicineHoustonTexasUSA Lewis katz School of Medicine Temple UniversityPhiladelphiaPennsylvaniaUSA Department of Neuroscience University ofMinnesotaMinneapolisMinnesotaUSA

Objectives:The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well *** quantified long‐term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ***:Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to *** on patient demographics and postoperative treatment with nasal saline irrigation twice daily with and without dissolved steroids (mometasone or budesonide) was ***,and 1‐,3‐,6‐,12‐,18‐,and 24‐month postoperative Sino‐Nasal Outcome Test (SNOT‐22) scores were ***:A total of 727 patients were assessed (53.4% males),with 479 patients in the no SI group and 248 patients in the SI *** SNOT‐22 scores did not differ significantly (P = 0.19).1‐,3‐,6‐,12‐,18‐,and 24‐month post‐op SNOT‐22 scores did not significantly differ between ***,mometasone irrigations resulted in significantly lower postoperative 2‐year SNOT‐22 scores compared to budesonide (P < 0.01) and saline (P = 0.03).Conclusions:Though corticosteroid irrigations are routine in managing inflammatory sinus disease,their role in postoperative management after ESBS for tumors is *** findings suggest that mometasone irrigation may be effective at improving postoperative quality of life in patients after ESBS.

关键词： postoperative steroid irrigations skull base tumors

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Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria:a meta-analysis of 18,421 patients

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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 78-93,I0009-I0013页

作者： Jin Hean koh Darren Jun Hao Tan Yuki Ong Wen Hui Lim Cheng Han Ng Phoebe Wen Lin Tay Jie Ning Yong Mark D.Muthiah Eunice X.Tan Ning Qi Pang Beom kyung kim Nicholas Syn Alfred kow brian k.P.Goh Daniel Q.Huang Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore Division of Gastroenterology and Hepatology Department of MedicineNational University HospitalSingaporeSingapore National University Centre for Organ Transplantation National University Health SystemSingaporeSingapore Division of Hepatobiliary&Pancreatic Surgery Department of SurgeryNational University HospitalSingaporeSingapore Department of Internal Medicine Yonsei University College of MedicineSeoulRepublic of Korea Yonsei Liver Center Severance HospitalYonsei University Health SystemSeoulRepublic of Korea Biostatistics and Modelling Domain Saw Swee Hock School of Public HealthNational University of Singapore and National University Health SystemSingaporeSingapore Department of Hepato-Pancreato-Biliary and Transplant Surgery Division of SurgerySingapore General HospitalSingaporeSingapore Liver Transplant Service SingHealth Duke-NUS Transplant CentreSingaporeSingapore

Background:Outcomes after liver resection(LR)and liver transplantation(LT)for hepatocellular carcinoma(HCC)are heterogenous and may vary by region,over time periods and disease *** aimed to compare overall survival(OS)and disease-free survival(DFS)between LT versus LR for HCC within the Milan ***:Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan ***-analyses and meta-regression were conducted using random-effects ***:We screened 2,278 studies and included 35 studies with 18,421 *** was associated with poorer OS[hazard ratio(HR)=1.44;95%confidence interval(CI):1.14-1.81;Pk of recurrence after LR is threefold that of LT.

关键词： Hepatocellular carcinoma(HCC) liver resection(LR) liver transplant survival recurrence

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Antilisterial Activity of Lactose Fatty Acid Esters in Milk

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Food and Nutrition Sciences 2019年第7期10卷 750-760页

作者： Seung-Min Lee brian Nummer brian Nummer Ashwini Wagh Marie k. Walsh Department of Nutrition Dietetics and Food Sciences Utah State University Logan Utah USA The Clorox Service Company Pleasanton California USA

Carbohydrate fatty acid esters have been shown to inhibit the growth of bacteria in growth media. In this study, the antilisterial activities of the carbohydrate esters lactose monodecanoate (LMD) and lactose monolaurate (LML) were tested in milk samples with variable fat content (up to 10%) and at different temperatures (37°C, 24°C and 5°C) after inoculation with a 5-strain Listeria monocytogenes cocktail. Both LMD and LML demonstrated antilisterial properties against L. monocytogenes in milk, with the observed log reductions in the LMD milk samples being higher than those in the LML samples at all tested temperatures. LMD in 1% and 2% fat milk was found to be bactericidal with no Listeria growth by day 6. LMD showed significant antilisterial activity in milk samples containing up to 9% fat at 37°and in samples with up to 3.5% fat at 24°C and in milk samples with up to 2% fat at 5°C. LML showed significant Listeria log reductions at 37°C with milk containing up to 9% fat but showed no microbial inhibition in milk in any samples at 24°C and 5°C. Although carbohydrate fatty acid esters have proven microbial bactericidal/bacteriostatic properties in growth media, their antimicrobial properties are reduced in a food system containing fat and at temperatures lower than 37°C. The significance of this research is identifying food constituents and storage temperatures that limit the microbial inhibitory properties of lactose esters to ensure appropriate use as potential food grade antilisterial agents.

关键词： Lactose Monodecanoate Lactose Monolaurate Antilisterial Activity Milk Fat Temperature

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Information point and saturation flow at signalized intersections

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Journal of Traffic and Transportation Engineering(English Edition) 2016年第4期3卷 336-344页

作者： Lijun Gao Bhuiyan M. Alam brian W. Randolph Douglas k. Nims Richard S. Martinko Department of Civil Engineering University of Toledo Toledo OH 43606 USA Department of Geography and Planning University of Toledo Toledo OH 43606 USA College of Engineering University of Toledo Toledo OH 43606 USA Richard Martinko Consulting Maumee OH 43537 USA

This paper introduces an information point factor and attempts to identify how it affects saturation flow and their relationship at signalized intersections. An information point is defined as any object, structure, or activity located outside of a traveling vehicle that can potentially attract the visual attention of the driver. Saturation flow rates are studied at three pairs of signalized intersections in Toledo, Ohio, USA. Each pair of intersections consists of one intersection with a high number of information points and one intersection with a low number of information points. Study results reveal that, for each pair of intersections, the one with high information points has a lower saturation flow rate than the one with low information points. A statistical analysis shows that the differences are significant. Based on the saturation flow data of the paired intersections, information point effect models are developed and presented in this paper.

关键词： Saturation flowInformation pointVisual distractionDriving behaviorTrip generationSignalized intersection

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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

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Harry Potter and the prisoner of Azkaban

Harry Potter and the prisoner of Azkaban

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作者： by J.k. Rowling illustrations by Mary GrandPr鈋 cover illustration by brian Selznick.

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Retinopathy of prematurity： an epidemic in the making

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Chinese Medical Journal 2010年第20期123卷 2929-2937页

作者： Graham E. Quinn Clare Gilbert brian A. Darlow Andrea Zin Children's Hospital of Philadelphia University of Pennsylvania Philadelphia Pennsylvania USA Intemational Centre for Eye Health London School of Hygiene and Tropical Medicine London UK Department of Paediatrics University of Otago Christchurch. Christchurch New Zealand Instituto Fernandes Figuera FIOCRUZ Rio de Janeiro Brazil

Objective To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity （ROP）,which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are *** sources The data used in this review were mainly from Medline and PubMed published in English. The search term was ＂retinopathy of prematurity and premature birth＂.Study selection We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature *** Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventiing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however,there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great *** ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be p

关键词： retinopathy of prematurity premature birth blindness childhood

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IL-10 Inhibits LPS-Induced Expression of miR-147 in Murine Macrophages

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Advances in Biological Chemistry 2014年第4期4卷 261-273页

作者： Leah N. Cardwell brian k. Weaver Department of Biology Missouri State University Springfield USA

Interleukin-10 (IL-10) mediates an anti-inflammatory response that constrains immune responses and limits inflammation-associated pathology. IL-10 does so, in part, by selectively inhibiting pro-inflammatory cytokine and chemokine expression induced in macrophages in response to Toll-like receptor (TLR) signaling. The IL-10-mediated anti-inflammatory response is executed through the activation of STAT3 leading to induction of target genes referred to as IL-10-induced genes. As miRNAs have emerged as important negative regulators of gene expression in various systems, we sought to address whether the IL-10-mediated anti-inflammatory response acts through regulated expression of miRNA genes. Using quantitative PCR-based arrays, we examined 140 miRNA genes with putative roles in inflammation for changes in expression in response to IL-10 and lipopoly-saccharide (LPS) in primary mouse macrophages. IL-10 stimulation resulted in the inhibition of miR-147 expression induced in response to LPS, while having a potentiating effect on the induction of miR-455. miR-147 is the second TLR-induced miRNA, in addition to miR-155, identified to be counter-regulated by IL-10. Its suppression by IL-10 suggests that miR-147 may have an unknown pro-inflammatory function in TLR-triggered macrophages. The results extend the notion that IL-10 selectively regulates expression of miRNA genes, and that miRNA-mediated pathways are a component of the IL-10-mediated anti-inflammatory response.

关键词： IL-10 Lipopolysaccharide Macrophage Inflammation MicroRNA

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