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Temporal epigenetic modifications differentially regulate ES cell-like colony formation and maturation

Stem Cell Discovery 2012年第2期2卷 45-57页

作者： j.ng S. Rim Karen L. Strickler Christian W. Barnes Lettie L. Harkins j.roslaw Staszkiewicz j.ffrey M. Gimble Gregory H. Leno kenneth j. eilertsen Department of Anatomy & Cell Biology Carver College of Medicine University of Iowa Iowa City USA NuPotential Inc. Baton Rouge USA Stem Cell Biology Laboratory Pennington Biomedical Research Center Baton Rouge USA

Human somatic cells can be directly reprogrammed to induced pluripotent stem (iPS) cells by forced expression of the transcription factors Oct4, Sox2, and either Klf4 and cMyc or Nanog and Lin28, using virus-based systems. However, low reprogramming efficiency and the potential for deleterious virus-induced genomic modification limit the clinical potential of this technology. Recent reports indicate, however, that the generation of iPS cells can be enhanced by the addition of synthetic small molecules, including epigenetic modulators. In this report, we demonstrate that the epigenetic modifiers Valproic Acid (VPA) and 5-azacytidine activate the reciprocal transcriptional regulation of endogenous pluripotency transcription factor genes in human dermal fibroblasts and that VPA alone can directly activate endogenous Oct4 in the absence of transgenes. Moreover, using human adipose cells, we demonstrate that histone deacetylase inhibition, prior to reprogramming factor transfection, increases embryonic stem (ES) cell-like colony formation ~2 - 3 fold. In addition, DNA methyltransferase (DNMT) inhibition during human ES cell culture promotes maturation of reprogrammed somatic cells, increasing the yield ~4 fold. These data provide proof of principle that reprogramming efficiency can be improved by inhibiting specific repressive epigenetic regulatory components at the levels of ES cell-like colony formation and maturation. In addition, these studies raise the interesting possibility that a more efficient small molecule-based reprogramming system may provide a superior alternative to current virus-based approaches.

关键词： Epigenetic Modification Somatic Cell Reprogramming

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Reprogramming mouse ear mesenchymal stem cells (EMSC) expressing the Dlk1-Dio3 imprinted gene cluster

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Stem Cell Discovery 2013年第1期3卷 64-71页

作者： Ru Gao j.ng S. Rim Karen L. Strickler Christian W. Barnes Lettie L. Harkins j.roslaw Staszkiewicz j.ffery M. Gimble Barbara Gawronska-Kozak Gregory H. Leno kenneth j. eilertsen Department of Anatomy & Cell Biology Carver College of Medicine University of Iowa Iowa City USA Institute of Animal Reproduction and Food Research of Polish Academy of Sciences Olsztyn Poland NuPotential Inc. Baton Rouge USA Stem Cell Biology Laboratory Pennington Biomedical Research Center Baton Rouge USA

The identification of a single, early marker for full developmental potential of induced pluripotent stem (iPS) cells has proven elusive. Recently, however, activation of the imprinted gene cluster, Dlk1-Dio3 has emerged as a viable candidate in the mouse. To explore the relationship between Dlk1-Dio3 expression and developmental potential more fully, we used murine ear mesenchymal stem cells (mEMSC) for iPS cell induction. Mouse EMSC are easily obtained and share functional characteristics with embryonic stem (ES) cells and therefore, may be a reliable non-embryonic source for iPS cell production. We report that mEMSC express high levels of Gtl2, a maternally expressed gene within the Dlk1-Dio3 imprinted cluster. Moreover, mEMSC produce Gtl2 expressing (Gtl2on) iPSC clones that share functional characteristics with ES cell clones. The production of Gtl2on iPS cell clones from mEMSC provides a new model with which to investigate the regulation of Dlk1-Dio3 cluster activity during direct cell reprogramming.

关键词： iPSCs Reprogramming Pluripotent Stem Cell

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Why ecosystem characteristics predicted from remotely sensed data are unbiased and biased at the same time-and how this affects applications

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Forest Ecosystems 2024年第1期11卷 24-31页

作者： Goran Ståhl Terj. Gobakken Svetlana Saarela Henrik j.Persson Magnus Ekstrom Sean P.Healey Zhiqiang Yang j.han Holmgren Eva Lindberg kenneth Nystrom Emanuele Papucci Patrik Ulvdal Hans OleØrka Erik Næsset Zhengyang Hou Håkan Olsson Ronald E.McRoberts Department of Forest Resource Management Swedish University of Agricultural Sciences90183UmeåSweden Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesÅsNorway USDA Forest Service Rocky Mountain Research StationOgdenUTUSA The Key Laboratory for Silviculture and Conservation of Ministry of Education Beijing Forestry UniversityBeijing100083China Department of Forest Resources University of MinnesotaSt.PaulMNUSA

Remotely sensed data are frequently used for predicting and mapping ecosystem characteristics,and spatially explicit wall-to-wall information is sometimes proposed as the best possible source of information for ***,wall-to-wall information typically relies on model-based prediction,and several features of model-based prediction should be understood before extensively relying on this type of *** such feature is that model-based predictors can be considered both unbiased and biased at the same time,which has important implications in several areas of *** this discussion paper,we first describe the conventional model-unbiasedness paradigm that underpins most prediction techniques using remotely sensed(or other)auxiliary *** this point of view,model-based predictors are typically ***,we show that for specific domains,identified based on their true values,the same model-based predictors can be considered biased,and sometimes severely *** suggest distinguishing between conventional model-bias,defined in the statistical literature as the difference between the expected value of a predictor and the expected value of the quantity being predicted,and design-bias of model-based estimators,defined as the difference between the expected value of a model-based estimator and the true value of the quantity being *** show that model-based estimators(or predictors)are typically design-biased,and that there is a trend in the design-bias from overestimating small true values to underestimating large true ***,we give examples of applications where this is important to acknowledge and to potentially make adj.stments to correct for the design-bias *** argue that relying entirely on conventional model-unbiasedness may lead to mistakes in several areas of application that use predictions from remotely sensed data.

关键词： Bias Model-based inference Design-based inference

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Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer *** remains elusive how CTCs evade immune surveillance and elimination by immune *** this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer ***,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in ***,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune ***,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yuj.e Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu kenneth Kin Wah To Chenglai Xia j.anye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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Adding Value to Crop Production Systems by Integrating Forage Cover Crop Grazing

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American j.urnal of Plant Sciences 2024年第3期15卷 180-192页

作者： Robert B. Mitchell Daren D. Redfearn kenneth P. Vogel Terry j. Klopfenstein Galen Erickson P. Stephen Baenziger Bruce E. Anderson Mary E. Drewnoski j.y Parsons Steven D. Masterson Marty R. Schmer Virginia L. j.n USDA-ARS Wheat Sorghum and Forage Research Unit University of Nebraska-Lincoln Lincoln NE USA Department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE USA Department of Animal Science University of Nebraska-Lincoln Lincoln NE USA Department of Agricultural Economics University of Nebraska-Lincoln Lincoln NE USA USDA-ARS Agroecosystem Management Research Unit University of Nebraska-Lincoln Lincoln NE USA

In addition to their value as cereal grains, wheat (Triticum aestivum L.) and triticale (× Triticosecale Wittmack) are important cool-season annual forages and cover crops. Yearling steer (Bos taurus) performance was compared in the spring following autumn establishment as for age cover crops after soybean [Glycine max (L.) Merr.] grain harvest. Replicated pastures (0.4 ha) were no-till seeded in three consecutive years into soybean stubble in autumn, fertilized, and grazed the following spring near Ithaca, NE, USA. Each pasture (n = 3) was continuously stocked in spring with four yearling steers (380 ± 38 kg) for 17, 32, and 28 d in 2005, 2006, and 2007, respectively. In 2005, average daily gain (ADG) for steers grazing triticale exceeded the ADG for wheat by 0.31 kghd-1d-1. In 2006, wheat ADG exceeded that for triticale by 0.12 kghd-1d-1. In 2007, steers grazing wheat lost weight, while steers grazing triticale gained 0.20 kghd-1d-1. Based on the 3-year average animal gains valued at $1.32 kg-1, mean net return ($ ha-1 yr-1) was $62.15 for triticale and $22.55 for wheat. Since these grazed cover crops provide ecosystem services in addition to forage, grazing could be viewed as a mechanism for recovering costs and adds additional value to the system. Based on this 3-year grazing trial, triticale was superior to wheat and likely will provide the most stable beef yearling performance across years with variable weather for the western Cornbelt USA.

关键词： Cover crops Soybean Triticale Wheat

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A decision framework for identifying models to estimate forest ecosystem services gains from restoration

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Forest Ecosystems 2016年第2期3卷 126-137页

作者： Zachary L. Christin kenneth j. Bagstad Michael A. Verdone Earth Economics 107 N Tacoma Ave Tacoma WA 98403 USA. U.S. Geological Survey Geosciences & Environmental Change Science Center Box 25046 MS 980 Denver CO 80225 USA. International Union for the Conservation of Nature 1630 Connecticut Ave. NW #300 Washington DC 20009 USA.

Restoring degraded forests and agricultural lands has become a global conservation priority. A growing number of tools can quantify ecosystem service tradeoffs associated with forest restoration. This evolving ＂tools landscape＂ presents a dilemma： more tools are available, but selecting appropriate tools has become more challenging. We present a Restoration Ecosystem Service Tool Selector （RESTS） framework that describes key characteristics of 13 ecosystem service assessment tools. Analysts enter information about their decision context, services to be analyzed, and desired outputs. Tools are filtered and presented based on five evaluative criteria： scalability, cost, time requirements, handling of uncertainty, and applicability to benefit-cost analysis. RESTS uses a spreadsheet interface but a web-based interface is planned. Given the rapid evolution of ecosystem services science, RESTS provides an adaptable framework to guide forest restoration decision makers toward tools that can help quantify ecosystem services in support of restoration.

关键词： Decision support Ecosystem services Forest restoration Modeling Valuation Comparative toolsassessment

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Global wild rice germplasm resources conservation alliance:World Wild-Rice Wiring

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Molecular Plant 2024年第4期17卷 516-518页

作者： Xiaoming Zheng Disna Ratnasekera j.ayu Fan Robert j.Henry Beng-Kah Song kenneth M.Olsen Bal Krishna j.shi Maria Celeste N.Banaticla-Hilario Tonapha Pusadee Adane Getachew Melaku Yeyinou Laura Estelle Loko Koukham Vilayheuang Gavers K.Oppong Samuel Aduse Poku Peterson W.Wambugu Song Ge Aldo Merotto j.nior Ohn Mar Aung Ramaiah Venuprasad Aj.y Kohli Wenbin Zhou Qian Qian National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Sanya National Research Institute of Breeding in Hainan Chinese Academy of Agricultural SciencesBeijing 100081China International Rice Research Institute DAPO Box 7777Metro Manila 4031Philippines Department of Agricultural Biology Faculty of AgricultureUniversity of RuhunaMatara 81000Sri Lanka Yazhouwan National Laboratory No.8 Huanjin RoadYazhou DistrictSanya CityHainan Province 572024China Hainan University Haikou 570228China ARC Centre of Excellence for Plant Success in Nature and Agriculture University of QueenslandBrisbaneQLD4072Australia School of Science Monash University Malaysia47500 Bandar SunwaySelangor 47500Malaysia Department of Biology Washington University in St.LouisSt.LouisMO 63130-4899USA National Agriculture Genetic Resources Center(Genebank) KhumaltarPO Box 3055KathmanduNepal Plant Biology Division Insttute of Biological SciencesUniversity of the Pilippines Los BanosLos BanosLaguna 4031Philippines Division of Agronomy Department of Plant and Soil SciencesFaculty of AgricultureChiang Mai UniversityChiang Mai 50200Thailand Bio and Emerging Technology Institute Addis Ababa 1165Ethiopia National University of Sciences TechnologiesEngineering and Mathematics(UNSTIM)Dassa-ZouméBP 14Benin National Genebank Rice and Cash Crops Research CenterNAFRIVientiane 0605Lao PDR Plant Sciences and the Bioeconomy Rothamsted ResearchHarpenden AL52JQUK UK Future Food Beacon of Excellence and School of Biosciences and University of Nottingham Nottingham LE125RDUK Department of Plant and Environmental Biology University of GhanaAccraGhana Kenya Agricultural and Livestock Research Organization Genetic Resources Research InstituteNairobi 00200Kenya Institute of Botany Chinese Academy of SciencesBeijing 100093China Federal University of Rio Grande do Sul UFRGSPorto Alegre 91501-970RSBrazil Department of Agricultur

Wild relatives of crop are key genetic resources serving as diversity reservoirs for crop improvement under changing ***(Oryza sativa)is one of the most important crops in the world,providing staple food for half of the world's *** rice is thus a critical germplasm resource for sustained global food security,ensuring high production yields,improved quality,and stress resistance in the face of climate *** rice is closely related to domesticated rice and has a rich genetic diversity and exceptional adaptability to extreme *** has played a pivotal role in the history of rice hybridization and has become a key resource for rice breeding *** identification of wild-type cytoplasmic male sterility resources paved the way for the achievement of the“three lines”goal in hybrid rice,leading to a significant increase in rice *** addition,the use of resistance alleles found in wild rice is making rice production more resilient to losses caused by environmental ***,wild rice germplasm resources are threatened due to habitat destruction and other anthropogenic *** the same time,the lack of centralized distribution of wild rice has hampered the sharing of basic information on wild rice resources and the utilization and conservation of wild rice in each country,as well as collaboration among scientists.

关键词： germplasm breeding crops

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Neurochemistry as a bridge between morphology and behavior： Perspectives on aggression in insects

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Current Zoology 2014年第6期60卷 778-790页

作者： Andrew N. BUBAK j.ime L. GRACE Michael j. WATT kenneth j. RENNER j.hn G. SWALLOW Neuroscience Program University of Colorado-Denver Anschutz Medical Campus Aurora CO 80045 USA Department of Integrative Biology University of Colorado-Denver Denver CO 80217-3364 USA Center for Brain and Behavior Research Basic Biomedical Sciences University of South Dakota Vermillion SD 57069 USA Department of Biology University of South Dakota Vermillion SD 57069 USA

Aggression is a common behavioral trait shared in many animals, including both vertebrates and invertebrates. However, the type and intensity of agonistic encounters and displays can vary widely both across and within species, resulting in complicated or subj.ctive interpretations that create difficulties in developing theoretical models that can be widely applied. The need to easily and obj.ctively identify quantifiable behaviors and their associated morphologies becomes especially important when attempting to decipher the neurological mechanisms underlying this complex behavior. Monoamines, neuropeptides, and pheromones have been implicated as important neuromodulators for agonistic displays in both invertebrates and vertebrates. Ad- ditionally, recent breakthroughs in insect research have revealed exciting proximate mechanisms important in aggression that may be broadly relevant, due to the relatively high conservation of these neurochemical systems across animal taxa. In this review, we present the latest research demonstrating the importance of monoamines, neuropeptides, and pheromones as neuromodulators for aggression across a variety of insect species. Additionally, we describe the stalk-eyed fly as a model system for studying aggres- sion, which integrates physiological, morphological, and neurochemical approaches in exploring detailed mechanisms responsible for this common yet complex behavior. We conclude with our perspective on the most promising lines of future research aimed at understanding the proximate and ultimate mechanisms underlying aggressive behaviors .

关键词： Monoamines Aggression Insects Evolutionary physiology Sexual Selection

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Kinematics, dynamics, and design of machinery / 2nd ed.

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2004年

作者： Waldron kenneth j.

来源：畅想之星图书光盘版（南... 评论

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