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Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation

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Bone Research 2018年第1期6卷 83-94页

作者： Heather A.Carey Blake E.Hildreth III Jennifer A.Geisler Mara C.Nickel Jennifer Cabrera Sankha Ghosh Yue Jiang Jing Yan James Lee Sandeep Makam Nicholas A.Young Giancarlo R.Valiente Wael N.Jarjour Kun Huang Thomas J.Rosol Ramiro E.Toribio julia f.charles Michael C.Ostrowski Sudarshana M.Sharma Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State University Wexner Medical Center College of Veterinary Medicine The Ohio State University Department of Biochemistry and Molecular Biology and Hollings Cancer Center Medical University of South Carolina Division of Rheumatology Immunology and Allergy Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Division of Rheumatology and Immunology Department of Internal Medicine The Ohio State University Wexner Medical Center Department of Biomedical Informatics The Ohio State University Wexner Medical Center

Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(Tf)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. functional genomic analysis indicated PU.1 and MITf orchestrated a Tf network essential for OC differentiation. Several of these Tfs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.

关键词： Genome-wide GWASs MITf

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Microfabricated polymer-metal biosensors for multifarious data collection from electrogenic cellular models

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Microsystems & Nanoengineering 2023年第2期9卷 167-180页

作者： charles M.Didier julia f.Orrico Omar S.Cepeda Trres Jorge Manrique Castro Aliyah Baksh Swaminathan Rajaraman NanoScience Technology Center University of Central Florida4353 Scorpius StreetResearch ISuite 231FL 32816 OrlandoUSA Burnett School of Biomedical Sciences University of Central Florida6900 Lake Nona BlvdFL 32827 OrlandoUSA Department of Biomedical Engineering Polytechnic University of Puerto Rico37700918Ponce de LeonSan JuanPuerto Rico Department of Electrical and Computer Engineering University of Central Florida4238 Scorpius StreetFL 32816 OrlandoUSA Department of Materials Science and Engineering University of Central Florida12760 Pegasus DriveEngineering ISuite 207FL 32816 OrlandoUSA

Benchtop tissue cultures have become increasingly complex in recent years,as more on-a-chip biological technologies,such as microphysiological systems(MPS),are developed to incorporate cellular constructs that more accurately represent their respective biological *** MPs have begun facilitating major breakthroughs in biological research and are poised to shape the field in the coming *** biological systems require integrated sensing modalities to procure complex,multiplexed datasets with unprecedented combinatorial biological *** this work,we expanded upon our polymer-metal biosensor approach by demonstrating a facile technology for compound biosensing that was characterized through custom modeling *** reported herein,we developed a compound chip with 3D microelectrodes,3D microfluidics,interdigitated electrodes(IDEs)and a *** chip was subsequently tested using the electrical/electrochemical characterization of 3D microelectrodes with 1 kHz impedance and phase recordings and IDE-based high-frequency(-1 MHz frequencies)impedimetric analysis of differential localized temperature recordings,both of which were modeled through equivalent electrical circuits for process parameter ***,a simplified antibody-conjugation strategy Was employed for a similar IDE-based analysis of the implications of a key analyte(L-glutamine)binding to the equivalent electrical ***,acute microfluidic perfusion modeling was performed to demonstrate the ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical ***,our work demonstrates the design,development,and characterization of an accessibly designed polymer-metal compound biosensor for electrogenic cellular constructs to facilitate comprehensive MPS data collection.

关键词： polymer recording breakthrough

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Environmental Impacts of the Yangtze Three Gorges Project: An Overview of the Chinese-German Research Cooperation

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Journal of Earth Science 2010年第6期21卷 817-823页

作者： Günter Subklew julia Ulrich Leander fürst Agnes Hltkemeier forschungszentrum Jülich GmbH

The construction of the Three Gorges Dam on the Yangtze River in China has a great influence on the ecosystems involved. In order to investigate these environmental effects in the Yangtze catchment area as well as downstream of the dam, forschungszentrum Julich has organized a research network for the Chinese and Germaa partners. In the research fields of （1） interaction water/ sediment/contaminants, （2） vegetation/biodiversity, （3） changing land use/erosion/mass movements, and （4） atmosphere, the partners have accumulated a great deal of expertise in handling major issues and also in developing models and recommendations for action. The following provides an overview of the research network and the research tasks. On the German side, five projects in research field （3） have been in operation since 2008. The results are reported in contributions by Ehret et al., Jaehnig and Cai, Schonbrodt et al., and Seeber et al.. Another five projects in research field （1） have started by September 2010. The research tasks undertaken in these five projects are presented below.

关键词： Three Gorges Dam Yangtze River environmental research ecosystem.

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机车车轮滑动的控制方法

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国外内燃机车 1985年第4期 29-34页

作者： f.charles 顾谦

本文提出一种控制电力机车或电传动内燃机车车轮滑动的方法和装置,以达到最佳的轮轨粘着。串激牵引电动机的某种特性,特别是反电势与电动机转速(转/分)之比值作为电动机电流的函数[E/n=f(I)],形成电压控制的基础,它限制供给每个牵引电... 详细信息

本文提出一种控制电力机车或电传动内燃机车车轮滑动的方法和装置,以达到最佳的轮轨粘着。串激牵引电动机的某种特性,特别是反电势与电动机转速(转/分)之比值作为电动机电流的函数[E/n=f(I)],形成电压控制的基础,它限制供给每个牵引电动机的电压(V)值,从而限制车轮滑动的最大百分数。选定的车轮滑动极限值几乎足以将大多数钢轨条件下的最大粘着条件包涵在内。将 E/n 与电动机的电压降(IR)、电动机的电流和机车速度的信号相结合,便导出无滑动状况下的理想的电压值 V。该电压随一个代表既定的最大滑动百分数的系数而增加,从而限制供给电动机的电压。一个最大电流电路包括从最大选定值减去允许的滑动百分数,以达到最大电动机电流值,从而获得最大牵引力。

关键词：牵引电动机串激转速限压串励车轮滑动百分数电流电阻器控制方法

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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika fujii charles f.Zorumski Yukitoshi Izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Re-evaluating the importance of carbohydrates as regenerative biomaterials

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Regenerative Biomaterials 2019年第1期6卷 1-12页

作者： Heidi f.Oldenkamp julia E.Vela Ramirez Nicholas A.Peppas Institute for Biomaterials Drug Deliveryand Regenerative Medicine McKetta Department of Chemical Engineering Department of Biomedical Engineering Department of Pediatrics Dell Medical School Department of Surgery and Perioperative Care Dell Medical School Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at AustinAustinTX 78712USA

Introduction Carbohydrates are the most abundant natural biomaterials in the *** interacting with cells of a variety of levels,they take part in essential functions of organisms including cellular communication,inflammation,infection development and *** carbohydrate–cell interactions occur on a variety of levels through glycoconjugates such as glycolipids,glycosaminoglycans(GAGs),glycoproteins and proteoglycans[1–4].The roles of carbohydrates in biological systems pose them as some of the most sought-after *** use of these multifaceted molecules provides the opportunity to tailor desired responses depending on the target application[1–5].

关键词： carbohydrate regenerative biomaterials polysaccharide tissue engineering

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell charles f.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao charles K.f.Chan Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of MedicineStanford CA 94305USA Department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA Department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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The evolution of Hessian fly from the Old World to the New World： Evidence from molecular markers

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Insect Science 2015年第6期22卷 768-784页

作者： Brandon J. Schemerhom Yan Ma Crane charles f. Crane USDA-ARS Department of Entomology Department of Botany and Plant Pathology Purdue University West Lafayette IN 47907USA

Eighteen polymorphic microsatellite loci and 11 single-nucleotide polymor- phisms were genotyped in 1 095 individual Hessian fly specimens representing 23 popula- tions from North America, southern Europe, and southwest Asia. The genotypes were used to assess genetic diversity and interrelationship of Hessian fly populations. While phyloge- netic analysis indicates that the American populations most similar to Eurasian populations come from the east coast of the United States, genetic distance is least between （Alabama and California） and （Kazakhstan and Spain）. Allelic diversity and frequency vary across North America, but they are not correlated with distance from the historically documented point of introduction in New York City or with temperature or precipitation. Instead, the greatest allelic diversity mostly occurs in areas with Mediterranean climates. The mi- crosatellite data indicate a general deficiency for heterozygotes in Hessian fly. The North American population structure is consistent with multiple introductions, isolation by dis- tance, and human-abetted dispersal by bulk transport of puparia in infested straw or on harvesting equipment.

关键词： allele frequency Hessian fly microsatellite population structure SNP SSR

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Deformation induced decoupling between U-Pb and trace elements in titanite revealed through petrochronology and study of localized deformation

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Geoscience frontiers 2023年第2期14卷 217-240页

作者： charles Kavanagh-Lepage félix Gervais Kyle Larson Riccardo Graziani Abdelali Moukhsil Département des génies civils géologiques et des minesPolytechnique MontréalMontréal H3T 1J4QuébecCanada Earth and Environmental Sciences IKBSASUniversity of British Columbia Okanagan3247 University WayKelownaBC V1V 1V7Canada Natural Resources Canada Government of Canada601 Booth St.OttawaON K1A 0E8Canada Direction de l’acquisition des connaissances géoscientifiques Ministère de l’Énergie et des Ressources naturelles du Québec57004e Avenue Ouest QuébecQC G1H 6R1QuébecCanada

In this contribution,we analyzed a pair of mafic samples collected from a recently identified shear zone and its proximal footwall from the Manicouagan Imbricate Zone(MIZ)of the central Grenville Province,Québec,*** petrochronology,metamorphic phase equilibria modelling,trace element thermometry,and electron backscattered diffraction data were used to define a Pressure-Temperature-timeDeformation path for the two *** interconnected dislocation network within titanite grains,as outlined with Kerneled Average Misorientation maps,are spatially correlated with variation in the U-Pb system but not with that observed for trace element These results suggest that the U-Pb system was decoupled from trace and rare earth elements and that deformation,rather than interface-coupled dissolution-precipitation reactions or re-crystallisation,was the main driver for this *** addition to highlighting a potential pitfall of titanite petrochronology,our P-T-t-D path reveals that ductile shear zones were active later than previously suggested within the MIZ.

关键词： Titanite petrochronology U-Pb Geochronology Phase equilibria modelling Trace elements Deformation Decoupling

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