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人类生命早期暴露组(HELIX)：项目理念与设计(待续)

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环境与职业医学 2015年第1期32卷 90-95页

作者： Martine Vrijheid Rémy Slama Oliver Robinson Leda Chatzi Muireann Coen Peter van den Hazel Cathrine Thomsen john Wright Toby j.Athersuch Narcis Avellana Xavier Basagana Celine Brochot Luca Bucchini Mariona Bustamante Angel Carracedo Maribel Casas Xavier Estivill Lesley Fairley Diana van Gent juan R.Gonzalez Berit Granum Regina Grazuleviiene Kristine B.Gutzkow jordi julvez Hector C.Keun Manolis Kogevinas Rosemary R.C.McEachan Helle Margrete Meltzer Eduard Sabidó PerE.Schwarze Valérie Siroux jordi Sunyer Elizabeth j.Want Florence Zeman mark j.nieuwenhuijsen 何蓉操仪汪源金泰廙 Centre for Research in Environmental Epidemiology(CREAL) Universitat Pompeu Fabra(UPF) CIBER Epidemiología y Salud Pública(CIBERESP) Institut National de la Santé et de la Recherche Médicale(INSERM) Institut Albert Bonniot(U823) University of Crete(UOC) Imperial College London(ICL) Veiligheids-en Gezondheidsregio Gelderland Midden(VGGM) Norwegian Institute of Public Health(NIPH) Bradford Institute for Health Research Bradford Teaching Hospitals NHS Foundation Trust(BTHFT) Sensing & Control Systems S.L(.S&C) Institut National de l’Environnement Industriel et des Risques(INERIS) Unit of Models for Ecotoxicology and Toxicology Hylobates Consulting S.R.L(.HYLO) Centre for Genomic Regulation(CRG) IMIM Hospital del Mar Research Insititute Grupo de Medicina Xenomica Fundación Pública Galega de Medicina Xeómica(SERGAS)CIBERERCEGENUniversidade de Santiago de Compostela Center of Excellence in Genomic Medicine Research King Abdulaziz University Vytauto Didziojo Universitetas(VDU)

[背景]人类在生命早期的发育期间可能特别容易受到环境暴露的影响。有关这一主题的人体研究一般集中在单一暴露与健康效应之间的关系。而"暴露组"的概念涵盖了从受孕开始的的全部暴露,完善了基因组。[目的]人类生命早期暴露组(HELIX)项... 详细信息

[背景]人类在生命早期的发育期间可能特别容易受到环境暴露的影响。有关这一主题的人体研究一般集中在单一暴露与健康效应之间的关系。而"暴露组"的概念涵盖了从受孕开始的的全部暴露,完善了基因组。[目的]人类生命早期暴露组(HELIX)项目是一个新的合作研究项目,目的是为了采用新的暴露评估和生物标志分析方法来描述生命早期多种环境因素的暴露,并将这些与生物标志组学和儿童健康结局相关联,从而刻画"生命早期暴露组"。本文描述了该项目的总体设计。[方法]HELIX将利用欧洲现有的6个出生队列研究来估计产前、产后暴露的一系列化学和物理暴露。建立全部队列中总共32 000对母亲和儿童的暴露模型,并在一个包含1 200对母亲和儿童的子队列中测量生物标志。嵌套重复采样的定组研究(n=150)将收集生物标志的变化数据,利用智能手机来评估流动性和体力活动,并监测个体暴露。采用组学技术确定与暴露相关的分子学特征(代谢组、蛋白质组、转录组和表观基因组)。对于多次暴露,采用统计方法估计胎儿和儿童的成长、肥胖、神经发育和呼吸系统结局中的暴露-效应关系。项目还将进行一项健康效应评估测试,以评价组合暴露的风险和收益。[结论]HELIX是描述欧洲人群生命早期暴露组并解开它与组学标志物和儿童健康之间关联的首次尝试之一。作为对暴露组学这一概念的验证,该项目向生命过程中暴露组迈出了重要的第一步。

关键词：人类生命早期暴露设计出生队列研究儿童健康生物标志效应评估生命早期

人类生命早期暴露组(HELIX)：项目理念与设计(续完)

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环境与职业医学 2015年第2期32卷 186-190页

作者： Martine Vrijheid Rémy Slama Oliver Robinson Leda Chatzi Muireann Coen Peter van den Hazel Cathrine Thomsen john Wright Toby j.Athersuch Narcis Avellana Xavier Basagana Celine Brochot Luca Bucchini Mariona Bustamante Angel Carracedo Maribel Casas Xavier Estivill Lesley Fairley Diana van Gent juan R.Gonzalez Berit Granum Regina Grazuleviiene Kristine B.Gutzkow jordi julvez Hector C.Keun Manolis Kogevinas Rosemary R.C.McEachan Helle Margrete Meltzer Eduard Sabidó Per E.Schwarze Valérie Siroux jordi Sunyer Elizabeth j.Want Florence Zeman mark j.nieuwenhuijsen 何蓉操仪汪源金泰廙 Centre for Research in Environmental Epidemiology(CREAL) Universitat Pompeu Fabra(UPF) CIBER Epidemiologíay Salud Pública(CIBERESP) Institut National de la Santé et de la Recherche Médicale(INSERM) Institut Albert Bonniot(U823) University of Crete(UOC) HeraklionCreteGreece Imperial College London(ICL) Veiligheids-en Gezondheidsregio Gelderland Midden(VGGM) Norwegian Institute of Public Health(NIPH) Bradford Institute for Health Research Sensing & Control Systems S.L.(S&C) Institut National de l’Environnement Industriel et des Risques(INERIS) Unit of Models for Ecotoxicology and Toxicology Hylobates Consulting S.R.L.(HYLO) RomeItaly Centre for Genomic Regulation(CRG) IMIM Hospital del Mar Research Insititute Grupo de Medicina Xenomica Fundación Pública Galega de Medicina Xeómica(SERGAS)CIBERERCEGENUniversidade de Santiago de CompostelaSantiago de CompostelaSpain Center of Excellence in Genomic Medicine Research King Abdulaziz UniversityJeddahKingdom of Saudi Arabia Vytauto Didziojo Universitetas(VDU) KaunusLithuania Bradford Institute for Health Research Bradford Teaching Hospitals NHS Foundation Trust(BTHFT)

3．2研究2：室外暴露传统h基于居住区评估的暴露，如室外空气污染、噪声、建筑环境，可以通过收集时间一空间活动以及（就空气污染而言）个人吸入空气量的信息，改善暴露评估和减小测量误差。例如，可替代吸入率（Kawahara等，2011）的... 详细信息

3．2研究2：室外暴露传统h基于居住区评估的暴露，如室外空气污染、噪声、建筑环境，可以通过收集时间一空间活动以及（就空气污染而言）个人吸入空气量的信息，改善暴露评估和减小测量误差。例如，可替代吸入率（Kawahara等，2011）的体力活动方面的信息与个人空气污染测量结合来评估吸入剂量。基于暴露评估的新一代地理信息系统（GIS）（Beelen等，2013;Eeflens等，2012）、遥感（Dadvand等，2012）和智能手机技术（deNazelle等，2013）使评估室外暴露和整合个人活动范围及体力活动数据变得更容易。

关键词：早期暴露人类生命地理信息系统设计空气污染测量误差体力活动建筑环境

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

儿童早期空气污染与呼吸道感染:ESCAPE项目中10个欧洲出生队列的分析

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环境与职业医学 2014年第3期31卷 202-202页

作者： Elaina A.MacIntyre Ulrike Gehring Anna Molter Elaine Fuertes Claudia Klümper Ursula Kramer Ulrich Quass Barbara Hoffmann Mireia Gascon Bert Brunekreef Gerard H.Koppelman Rob Beelen Gerard Hoek Matthias Birk johan C.de jongste H.A.Smit josef Cyrys Olena Gruzieva Michal Korek Anna Bergstrom Raymond M.Agius Frank de Vocht Angela Simpson Daniela Porta Francesco Forastiere Chiara Badaloni Giulia Cesaroni Ana Esplugues Ana Fernández-Somoano Aitana Lerxundi jordi Sunyer Marta Cirach mark j.nieuwenhuijsen Goran Pershagen joachim Heinrich

[背景]将交通源空气污染作为幼儿期呼吸道感染的危险因素的研究很少。[目的]在10个欧洲出生队列——BAMSE（瑞典）、GASPⅡ（意大利）、GINIplus和LISAplus（德国）、MAAS（英国）、PIAMA（荷兰）和4个INMA队列（西班牙）——中研究空... 详细信息

[背景]将交通源空气污染作为幼儿期呼吸道感染的危险因素的研究很少。[目的]在10个欧洲出生队列——BAMSE（瑞典）、GASPⅡ（意大利）、GINIplus和LISAplus（德国）、MAAS（英国）、PIAMA（荷兰）和4个INMA队列（西班牙）——中研究空气污染与肺炎、哮喘及中耳炎之间的相关性，并使用meta分析得出综合效应估值。[方法]评价家长报告的医师诊断的儿童早期肺炎、中耳炎以及哮喘与全年平均污染物水平[二氧化氮（NO2）、氮氧化物（NOx）、≤2．5gm的颗粒物（PM2.5）、PM2.5吸光度、PM10、PM2.5-10（粗PM）]间的关联，污染物浓度的估计采用土地利用回归模型并根据孩子的出生住址分配。作为ESCAPE项目的一部分，每个研究区域都采用相同的方案建立回归模型。用logistic回归来计算每个研究校正后的效应估值，用随机效应meta分析来计算合并的估计值。[结果]除了PM2.5外的所有污染物，肺炎的合并校正优势比（OR）均升高（例如，N02每增加10μg／m3，OR=1．30，95％CI：1．02～1．65；PM10每增加10μg／m3的OR=1．76，95％CI：1．00—3．09）。对于中耳炎和哮喘，除了NO2与中耳炎问的关联（每10μg／m3对应的OR=1．09，95％CI：1．02～1．16），所有分析的结果均无显著性。[结论]对ESCAPE项目中10个欧洲出生队列进行的meta分析为空气污染和儿童早期肺炎之间的相关性找到一致性的证据，也为与中耳炎间的相关性找到了一些证据。

关键词：早期肺炎呼吸道感染出生队列空气污染欧洲儿童 meta分析 logistic

Assessing ecological and physiological costs of melanism in North American Papilio glaucus females: two decades of dark morph frequency declines

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Insect Science 2020年第3期27卷 583-612页

作者： j.mark Scriber Department of Entomology Michigan State UniversityEast LansingMichiganUSA McGuire Center for Lepidoptera and Biodiversity Florida Museum of Natural HistoryUniversity of FloridaGainesvilleFloridaUSA

Polymorphisms for melanic form of insects may provide various selective ***,melanic alleles may have significant/subtle pleiotrophic“costs.”Several potential pleiotrophic effects of the W(=Y)‐linked melanism gene in Papilio glaucus L.(Lepidoptera)showed no costs for melanic versus yellow in adult size,oviposition preferences,fecundity,egg viability,larval survival/growth rates,cold stress tolerance,or postdiapause emergence *** selection(males choosing yellow rather than mimetic dark females)had been suggested to provide a balanced polymorphism in ***,but spermatophore counts in wild females and direct field tethering studies of size‐matched pairs of virgin females(dark and yellow),show that male preferences are random or frequency‐dependent from Florida to Michigan,providing no yellow counter‐*** frequency declines of dark(melanic/mimetic)females in *** populations are shown in several major populations from Florida(27.3°N latitude)to Ohio(38.5°N).Summer temperatures have increased significantly at all these locations during this time(1999–2018),but whether dark morphs may be more vulnerable(in any stage)to such climate warming remains to be *** potential reasons for the frequency declines in mimetic females are discussed:(i)genetic introgression of Z‐linked melanism suppressor genes from ***(R&j)and the hybrid species,***(Pavulaan&Wright),(ii)differential developmental incompatibilities,or Haldane effects,known to occur in hybrids,(iii)selection against intermediately melanic(“dusty”)females(with the W‐linked melanic gene,b+)which higher temperatures can cause.

关键词： climate warming ecology of melanism incomplete mimicry pleiotrophic costs

Integrating ancient patterns and current dynamics of insect-plant interactions＂ Taxonomic and geographic variation in herbivore specialization

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Insect Science 2010年第6期17卷 471-507页

作者： j. mark Scriber Department of Entomology Michigan State University East Lansing Michigan McGuire Center for Lepidoptera and Biodiversity Florida Museum of Natural History University of Florida Gainesville Florida USA

The search for pattern in the ecology and evolutionary biology of insect-plant associations has fascinated biologists for centuries. High levels of tropical （tow-latitude） plant and insect diversity relative to poleward latitudes and the disproportionate abundance of host-specialized insect herbivores have been noted. This review addresses several aspects of local insect specialization, host use abilities （and loss of these abilities with specialization）, host-associated evolutionary divergence, and ecological （including ＂hybrid＂） speciation, with special reference to the generation of biodiversity and the geographic and taxonomic identification of ＂species borders＂ for swallowtail butterflies （Papilionidae）. From ancient phytochemically defined angiosperm affiliations that trace back millions of years to recent and very local specialized populations, the Papilionidae （swallowtail butterflies） have provided a model for enhanced tmderstanding of localized ecological patterns and genetically based evolutionary processes. They have served as a useful group for evaluating the feeding specialization/physiological efficiency hypothesis. They have shown how the abiotic （thermal） environment interacts with host nutritional suitability to generate ＂voltinisrn/suitability＂ gradients in specialization or preference latitudinally, and geographical mosaics locally. Several studies reviewed here suggest strongly that the oscillation hypothesis for speciation does have considerable merit, but at the same time, some species-level host specializations may lead to evolutionary dead-ends, especially with rapid environmental/habitat changes involving their host plants. Latitudinal gradients in species richness and degree of herbivore feeding specialization have been impacted by recent developments in ecological genetics and evolutionary ecology. Localized insect- plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic speci

关键词： evolutionary dead-ends key innovations latitudinal gradients oscillation hypothesis of speciation polyspecialists preference/performance specialization/physiological efficiency hypothesis voltinism-suitability hypothesis

Impacts of climate warming on hybrid zone movement： Geographically diffuse and biologically porous ＂species borders＂

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Insect Science 2011年第2期18卷 121-159页

作者： j. mark Scriber Department of Entomology Michigan State University East Lansing Michigan McGuire Center for Lepidoptera and Biodiversity Flonda Museum of Natural History University of Florida Gainesville Florida USA

The ecology and evolutionary biology of insect-plant associations has real- ized extensive attention, especially during the past 60 years. The classifications （categorical designations） of continuous variation in biodiversity, ranging from global patterns （e.g., lat- itudinal gradients in species richness/diversity and degree of herbivore feeding specialization） to localized insect-plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic species, remain academically contentious. Semantic and biosystematic （taxonomical） disagreements sometimes detract from more important ecological and evolutionary processes that drive diversification, the dynamics of gene flow and local extinctions. This review addresses several aspects of insect specialization, host-associated divergence and ecological （including ＂hybrid＂） speciation, with special reference to the climate warming impacts on species borders of hybridiz- ing swallowtail butterflies （Papilionidae）. Interspecific hybrid introgression may result in collapse of multi-species communities or increase species numbers via homoploid hybrid speciation. We may see diverging, merging, or emerging genotypes across hybrid zones, all part of the ongoing processes of evolution. Molecular analyses of genetic mosaics and genomic dynamics with ＂divergence hitchhiking＂, combined with ecological, ethological and physiological studies of＂species porosity＂, have already begun to unveil some answers for some important ecological/evolutionary questions. （i） How rapidly can host-associated divergence lead to new species （and why doesn＇t it always do so, e.g., resulting in ＂incom- plete＂ speciation）？（ii） How might ＂speciation genes＂ function, and how/where would we find them？（iii） Can oscillations from specialists to generalists and back to specialists help explain global diversity in herbivorous insects？（iv） How could recombinant interspecific hybridization lead to divergence an

关键词： cryptic species divergence hitchhiking ecologiealspeciation host associateddivergence mosaic genomes range limits recombinant hybrid species phylogeography,polyspecialists species boundaries

A review of refinery complexity applications

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Petroleum Science 2017年第1期14卷 167-194页

作者： mark j. Kaiser Center for Energy Studies Louisiana State UniversityEnergy Coast and Environment Building Baton RougeLA 70803 USA

Refinery complexity quantifies the sophistication and capital intensity of a refinery and has found widespread application in facility classification, cost estimation, sales price models, and other uses. Despite the ubiquity and widespread use of refining complexity, however, surprisingly little material has been written on its applications. The pur- pose of this review is to describe the primary applications of refinery complexity and some recent extensions. A secondary purpose of this review is to provide a framework that unifies complexity applications and suggests avenues for future research. Examples illustrate the applications considered.

关键词： Cost estimation Functional complexityInverse problem Replacement cost Refineryclassification Sales price models

Segregation of F-2 interspecific hybrid growth performance and wing color patterns relative to parental species in the Papilio machaon species group （Lepidoptera： Papilionidae）

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Insect Science 2007年第5期14卷 389-400页

作者： j. mark SCRIBER Department of Entomology Michigan State University East Lansing Michigan USA

A strange Papilio female specimen with a prominent yellow wing band type very much like P. brevicauda （and also seen in P. machaon, and P. zelicaon） was captured in the forested mountains of southwest Vermont, USA. Despite its brevicauda-like appearance, it had mt-DNA of P. polyxenes. In eastern North America the P. brevicauda （Maritime Provinces of Canada） is currently believed to reflect previous （ancient） hybridization between ancestral P. machaon and P. polyxenes. It is uncertain whether the brevicauda-like wing trait features in the odd Vermont female may be a result of some introgression of P. machaon or P. brevicauda with P. polyxenes in eastern North America as seen also in the Ozark Mountains with P. joanae. Nonetheless, the significance of wing trait analyses in relation to hybrid zones with P. polyxenes remains relevant. The segregation of wing color patterns and hostplant use abilities （efficiencies and growth rates） were examined for laboratory hand-paired F-2 hybrids of P. zelicaon ~ Papilio polyxenes relative to the parental species and primary hybrids. The black adult color pattern characterizing P. polyxenes is presumed to be inherited as a simple autosomal dominant. These hybrids were examined to determine：（i） how F-1 primary hybrid offspring perform relative to the parental types in survival, growth rates, and growth efficiencies; and （ii） whether these larval traits and the adult color patterns might be linked with wing morphology in the F-2 hybrids. While the F-1 hybrids grew as well as the P. polyxenes parent （P. zelicaon was significantly less efficient and slower in growth than either of these）, we could not convincingly determine whether the growth performances of the F-2 segregants were linked with the parental wing patterns.

关键词： hybrid swarms feeding efficiencies autosomai trait genetics Papilio polyxenes,Papilio zelicaon Papilio brevicauda