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Bone Research 2014年第2期2卷 93-102页

作者： Kyu Sang Joeng Fanxin Long Department of medicine Washington University School of Medicine St Louis MO USA Division of Biology and Biomedical Sciences Washington University in St. Louis St Louis MO USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Department of Orthopaedic Surgery Washington University School of Medicine St Louis MO USA Department of Developmental Biology Washington University School of Medicine St Louis MO USA

Indian hedgehog （Ihh） is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes ost.oblast.differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test.the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh-/- mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh-/- mouse, but failed to rest.re orthotopic ost.oblast.differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh-/-; Gli3-/- embryo. Interest.ngly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.

关键词： bone Ihh Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not ost.oblast.differentiation during endochondral bo

Perioperative care in older adults

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Journal of Geriatric Cardiology 2015年第5期12卷 465-469页

作者： Giselle A Baquero Michael W Rich Penn st.te College of medicine Hershey PA USA washington university school of medicine St. Louis MO USA

1 Background Over the last.20 years, the number of older adults requiring surgical interventions has subst.ntially increased and will continue to escalate as the population ages. Perioperative management of older patients poses challenges not encountered in younger individuals. People over 70 years of age are more likely to have multiple comorbidities, physical and cognitive impairments, and reduced cardiac, pulmonary, and renal reserve. These factors predispose older patients to increased risk for perioperative complications and prolonged length of hospital st.y, which in turn increase risk for iatrogenesis, nosocomial infections, and perioperative mortality.

关键词： Aging Cardiovascular disease Perioperative care Surgery The elderly

Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Neversmokers

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 991-1013页

作者： Jennifer A.Karlow Erica C.Pehrsson Xiaoyun Xing Mark Watson Siddhartha Devarakonda Ramaswamy Govindan Ting Wang Department of Genetics Washington University School of MedicineSt.LouisMO 63110USA The Edison Family Center for Genome Sciences and Syst.ms Biology Washington University School of MedicineSt.LouisMO 63110USA Department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63110USA Department of medicine Washington University School of MedicineSt.LouisMO 63110USA McDonnell Genome Inst.tute Washington University School of MedicineSt.LouisMO 63108USA

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment *** determine the potential contribution of DNA methylation alterations to tumor phenotype in non-small cell lung cancer(NSCLC)in both smoker and never-smoker patients,we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays,methylated DNA immunoprecipitation sequencing(MeDIP-seq)and methylation sensitive rest.ic-tion enzyme sequencing(MRE-seq).We reported recurrent methylation changes in the promoters of several genes,many previously implicated in cancer,including FAM83A and SEPT9(hy-pomethylation),as well as PCDH7,NKX2-1,and SOX17(hypermethylation).Although many methylation changes between tumors and their paired normal samples were shared across patients,several were specific to a particular smoking *** example,never-smokers displayed a greater proportion of hypomethylated differentially methylated regions(hypoDMRs)and a greater number of recurrently hypomethylated promoters,including those of ASPSCRI,TOP2A,DPP9,and USP39,all previously linked to *** outside of promoters were also widespread and often recurrent,particularly methylation loss over repetitive elements,highly enriched for ERV1 *** hypoDMRs were enriched for several transcription factor binding motifs,often for genes involved in signaling and cell *** example,71%of recurrent promoter hypoDMRs contained a motif for ***,the majority of DMRs were located within an active chromatin st.te in tissues profiled using the Roadmap Epigenomics data,suggest.ng that methylation changes may contribute to altered regulatory programs through the adaptation of cell type-specific expression programs.

关键词： Non-small cell lung cancer Epigenomics M&M methylCRF DNA methylation

Review and Evaluate the Bioinformatics Analysis st.ategies of ATAC-seq and CUT&Tag Data

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 11-27页

作者： Siyuan Cheng Benpeng Miao Tiandao Li Guoyan Zhao Bo Zhang Department of Developmental Biology Center of Regenerative MedicineWashington University School of MedicineSt.LouisMO 63108USA Department of Genetics Washington University School of MedicineSt.LouisMO 63108USA Department of Neurology Washington University School of MedicineSt.LouisMO 63108USA Department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63108USA

Efficient and reliable profiling methods are essential to st.dy ***5,one of the first.identified prokaryotic transposases with high DNA-binding and tagmentation efficiency,is widely adopted in different genomic and epigenomic protocols for high-throughputly exploring the genome and *** on Tn5,the Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq)and the Cleavage Under Targets and Tagmentation(CUT&Tag)were developed to measure chromatin accessibility and detect DNA–protein *** methodologies can be applied to large amounts of biological samples with low-input levels,such as rare tissues,embryos,and sorted single ***,fast.and proper processing of these epigenomic data has become a bottleneck because massive data production continues to increase ***,inappropriate data analysis can generate biased or misleading ***,it is essential to evaluate the performance of Tn5-based ATAC-seq and CUT&Tag data processing bioinformatics tools,many of which were developed most.y for analyzing chromatin immunoprecipitation followed by sequencing(ChIP-seq)***,we conducted a comprehensive benchmarking analysis to evaluate the performance of eight popular software for processing ATAC-seq and CUT&Tag *** compared the sensitivity,specificity,and peak width dist.ibution for both narrow-type and broad-type peak *** also test.d the influence of the availability of control IgG input in CUT&Tag data ***,we evaluated the differential analysis st.ategies commonly used for analyzing the CUT&Tag *** st.dy provided comprehensive guidance for selecting bioinformatics tools and recommended analysis st.ategies,which were implemented into Docker/Singularity images for st.eamlined data analysis.

关键词： Tn5 transposase Epigenetic Bioinformatics ATAC-seq CUT&Tag

Tumor organoids to st.dy gast.oesophageal cancer: a primer

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Journal of Molecular Cell Biology 2020年第8期12卷 593-606页

作者： Ramon U.Jin Jason C.Mills Division of Oncology Department of Internal MedicineWashington University School of MedicineSt.LouisMO 63130USA Division of Gast.oenterology Department of Internal MedicineWashington University School of MedicineSt.LouisMO 63130USA Department of Developmental Biology Washington University School of MedicineSt.LouisMO 63130USA Department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63130USA

Gast.oesophageal cancers are leading causes of cancer *** attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and *** is dear that we should no longer treat all gast.oesophageal cancers as a homogeneous disease,which is what we do when we use nonspecific ***,we currently cannot monitor successful gene/pathway targeting,nor underst.nd how/when tumors develop resist.nce,nor predict which patients will derive maximal *** improve outcomes,we must.precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to st.dy and predict treatment effects in individual *** this end,patient-derived organoids,in which tumor cells from individual patients are grown in a Petri dish,are a new versatile syst.m that allows for timely expandability,detailed molecular characterization,and genetic manipulation with the promise of enabling predictive assessment of treatment *** this review,we will explore the development and basic techniques for organoid generation,and discuss the current and potential future applications of this exciting technology to st.dy the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.

关键词： targeted therapy precision oncology cancer model tumor heterogeneity cancer evolution personalized medicine

Dielectric microspheres enhance microscopy resolution mainly due to increasing the effective numerical aperture

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Light(Science & Applications) 2023年第1期12卷 17-19页

作者： Arash Darafsheh Vahid Abbasian Department of Radiation Oncology Washington University School of Medicine in St.LouisSt.LouisMO 63110USA

Microsphere-assist.d microscopy utilizing a microsphere in immediate proximity of the specimen boost. the imaging resolution mainly as a result of an increase in the effective numerical aperture of the syst.m.

关键词： resolution numerical utilizing

Rapid climate change-induced collapse of hunter-gatherer societies in the lower Mississippi River valley between ca. 3300 and 2780 cal yr BP

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Science China Earth Sciences 2018年第2期61卷 178-189页

作者： trist.am r.kidder edward r.henry lee j.arco Department of Anthropology Washington University in St. Louis St. Louis 63130 USA Geoarehaeology Laboratory Washington University in St. Louis St. Louis 63130 USA GAI Consultants Inc. Homestead PA 15120 USA Teaching and Experimental Center for Archaeology and Cultural Heritage Protection Henan University Kaifeng 475001 China

Hunter-gatherer communities in the American Southeast.reached an apogee of social and political complexity in the period between ca. 4200 and 3000 cal yr BP. In the lower Mississippi Valley(LMV) the Poverty Point culture defined this period of socio-political elaboration. However, following a significant period of climate change that led to exceptional flooding and a major reorganization of the course of the Mississippi River, this culture collapsed beginning ca. 3300–3200 cal yr BP and the LMV was abandoned for the subsequent 500 years. In this st.dy, we use data from the Jaketown site in the Yazoo Basin of west.central Mississippi to refine the chronology of the climate event that caused the collapse of the Poverty Point culture. A large flood buried Poverty Point-era occupation deposits at Jaketown around 3310 cal yr BP. Lateral migration of the Mississippi River during flooding led to inundation of the Yazoo Basin and re-occupation of ancient river courses. A coarse sand st.atum topped by a more than a meter-thick fining upward sediment package marks a crevasse deposit caused by a rupture of the natural levee at Jaketown. This levee breach was part of a larger pattern of erratic flooding throughout the LMV and is associated with major landscape evolution and the abandonment of Poverty Point sites within the valley. Early Woodland peoples re-colonized the crevasse surface after ca. 2780 cal yr BP. Following this event, the Jaketown site and the east.rn Yazoo Basin witnessed a period of landscape st.bility that last. to this day. These archaeological data demonst.ate how climate change and natural disast.rs can lead to socio-political dissolution and reorganization even in relatively small-scale hunter-gatherer populations.

关键词： Rapid climate change Hunter-gatherers Flooding Mississippi River Valley Poverty Point Jaketown site

Tissue-specific features of innate lymphoid cells in antiviral defense

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Cellular & Molecular Immunology 2024年第9期21卷 1036-1050页

作者： Sytse J.Piersma Division of Rheumatology Department of MedicineWashington University School of MedicineSt.LouisMO63110USA Siteman Cancer Center Washington University School of MedicineSt.LouisMO63110USA

Innate lymphocytes(ILCs)rapidly respond to and protect against.invading pathogens and *** include natural killer(NK)cells,ILC1s,ILC2s,ILC3s,and lymphoid tissue inducer(LTi)cells and include type I,type II,and type III immune *** NK cells have been well recognized for their role in antiviral immunity,other ILC subtypes are emerging as players in antiviral *** ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host.depending on the tissue *** review focuses on the specialized functions of each ILC subtype and their roles in antiviral immune responses across *** viruses within infection-prone tissues will be highlighted to provide an overview of the extent of the ILC immunity within tissues and emphasize common versus virus-specific responses.

关键词： NK cell innate lymphoid cell tissue microenvironment virus infection anti-viral immunity

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 272-276页

作者： Marta Celorrio Kirill Shumilov st.art H.Friess Department of Pediatrics Washington University in St.Louis School of MedicineSt.LouisMOUSA

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental ***,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic st.ategies targeted to address one clinical concern causing unintended effects in other remote organ *** the bidirectional communication between the gast.ointest.nal tract and the brain has been shown to influence both the central nervous syst.m and gast.ointest.nal tract homeost.sis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut *** in gut microbial populations in the setting of central nervous syst.m disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient *** this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain *** will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

关键词： gut microbiome gut microbiota gut-brain axis macrophage microglia monocyte neuroinflammation short-chain fatty acids T cell traumatic brain injury

Type 2 immunity in the brain and brain borders

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Cellular & Molecular Immunology 2023年第11期20卷 1290-1299页

作者： Tornike Mamuladze Jonathan Kipnis Center for Brain Immunology and Glia(BIG) Washington University in St.LouisSt.LouisMO63110USA Department of Pathology and Immunology School of MedicineWashington University in St.LouisSt.LouisMO63110USA Immunology Graduate Program School of MedicineWashington University in St.LouisSt.LouisMO63110USA

Recent research in neuroimmunology has revolutionized our underst.nding of the intricate interactions between the immune syst.m and the central nervous syst.m(CNS).The CNS,an“immune-privileged organ”,is now known to be intimately connected to the immune syst.m through different cell types and *** type 2 immune responses have traditionally been associated with allergy and parasitic infections,emerging evidence suggest. that these responses also play a crucial role in CNS homeost.sis and disease *** 2 immunity encompasses a delicate interplay among st.oma,Th2 cells,innate lymphoid type 2 cells(ILC2s),mast.cells,basophils,and the cytokines interleukin(IL)-4,IL-5,IL-13,IL-25,TSLP and *** this review,we discuss the beneficial and detrimental roles of type 2 immune cells and cytokines in CNS injury and homeost.sis,cognition,and diseases such as tumors,Alzheimer’s disease and multiple sclerosis.

关键词： Type 2 immunity Meningeal immunity Neuroimmunology