Analysis of medaka cytochrome P450 3A homotropic and heterotropic cooperativity

We have previously demonstrated that medaka CYP3A is associated with metabolism of several endobiotics including steroids and bile acids. In this study, we demonstrate that medaka CYP3A catalysis exhibits unusual kinetic behaviors consistent with allosteric interaction which cannot be described by hyperbolic kinetic models. Using 7-benzyloxy-4-(trifluoromethyl)-coumarin (BFC) and nonylphenol as CYP3A substrates, we describe both homotropic and heterotropic cooperative interactions. Given the role of CYP3A in maintaining the homeostatic balance for numerous endobiotics, enzymatic activation/inhibition by endocrine disruptors (EDCs) represents a putative (non-genomic) mechanism for endocrine disruption.     

Histopathological biomarkers in estuarine fish species for the assessment of biological effects of contaminants

The increasing emphasis on the assessment and monitoring of estuarine ecosystems has highlighted the need to deploy appropriate biological indices for these locations. Fish diseases and histopathology, with a broad range of causes, are increasingly being used as indicators of environmental stress since they provide a definite biological end-point of historical exposure. This study reports on the histopathological alterations observed in selected organs and tissues of three species of estuarine fish (Platichthys flesus, Pomatoschistus minutus and Zoarces viviparus), captured from four British estuaries (the Tyne, Tees, Mersey and Alde), differently impacted by contaminants, including PAHs. A biannual sampling regime was used to identify the important seasonal variations that occur in terms of the observed biological effects. Inflammatory lesions and hepatocellular fibrillar inclusions attained their highest prevalence in P. flesus captured from the Tyne, Tees and Mersey. The presence of pre-neoplastic and neoplastic toxicopathic lesions was highest in P. flesus captured from these sites, when compared to fish from the Aide reference site. In particular, the prevalence of hepatic foci of cellular alteration (up to 43.3%) and hepatocellular adenoma (up to 10%) were highest in P. flesus captured from the Mersey estuary. Intersex (ovotestis) was only recorded in male P.flesus captured from the Mersey estuary (up to 8.3%) and from male Z. viviparous captured from the Tyne estuary (25%). Pathologies associated with the gill and the kidney were also most prevalent in fish captured from the Tyne, Tees and Mersey estuaries. This study has successfully applied histopathology to an estuarine monitoring program, both for the recording of toxicopathic lesions in the liver and other organs, and for the detection of the endpoint of endocrine disruption, intersex. As such, it provides a powerful integrative tool for the assessment of biological effects of contaminants in these environments.     

Abrupt climate change and transient climates during the Paleogene: a marine perspective

Detailed investigations of high latitude sequences recently collected by the Ocean Drilling Program (ODP) indicate that periods of rapid climate change often culminated in brief transient climates, with more extreme conditions than subsequent long term climates. Two examples of such events have been identified in the Paleogene; the first in latest Paleocene time in the middle of a warming trend that began several million years earlier: the second in earliest Oligocene time near the end of a Middle Eocene to Late Oligocene global cooling trend. Superimposed on the earlier event was a sudden and extreme warming of both high latitude sea surface and deep ocean waters. Imbedded in the latter transition was an abrupt decline in high latitude temperatures and the brief appearance of a full size continental ice-sheet on Antarctica. In both cases the climate extremes were not stable, lasting for less than a few hundred thousand years, indicating a temporary or transient climate state. Geochemical and sedimentological evidence suggest that both Paleogene climate events were accompanied by reorganizations in ocean circulation, and major perturbations in marine productivity and the global carbon cycle. The Paleocene-Eocene thermal maximum was marked by reduced oceanic turnover and decreases in global delta 13C and in marine productivity, while the Early Oligocene glacial maximum was accompanied by intensification of deep ocean circulation and elevated delta 13C and productivity. It has been suggested that sudden changes in climate and/or ocean circulation might occur as a result of gradual forcing as certain physical thresholds are exceeded. We investigate the possibility that sudden reorganizations in ocean and/or atmosphere circulation during these abrupt transitions generated short-term positive feedbacks that briefly sustained these transient climatic states.     

滇黔桂微细浸染型金矿铅同位素组成及应用

滇黔桂微细浸染型金矿铅同位素组成及应用＊刘显凡刘家军朱赖民（中国科学院地球化学研究所，贵阳５５０００２）卢秋霞（成都理工学院，成都６１００５９）关键词微细浸染型金矿铅同位素组成矿质来源上地幔分异混染滇黔桂１矿床地质背景研究区位于扬子地台西南缘与华南加...     

东淮噶尔锡矿带锆石标型特征与含矿性关系及成因意义

锡矿成矿带赋存于海西期花岗岩体中,沿卡拉麦里构造带呈北北西向展布。矿床类型主要有钠长石化蚀变花岗岩型、石英脉型、云英岩脉型及钠闪石-石英脉型。矿体物质来源无疑是由花岗岩提供的。据岩石学和岩石化学的研究证实,花岗岩为多阶段、多期次的复式杂     

地幔流体的交代作用——来自碱性正长岩及其深源岩石包体的证据

滇西玉龙县小桥头硅化霓辉正长斑岩中,含有较多镁铁-超镁铁质深源包体岩石。经岩相学和电子探针及扫描电镜分析发现,伴随交代蚀变,寄主岩和各类镁铁-超镁铁质包体岩石中,普遍发育沿粒间和矿物晶体裂隙或解理纹贯入或穿插的黑色不透明物质,主要由微晶硅酸盐矿物和磁铁矿组成。本文研究认为,硅酸盐矿物与磁铁矿在背散射电子图像中表现为熔离特征,这种在透光显微镜下呈黑色不透明的微晶固体,是引发交代蚀变、具熔浆流体特点和超临界流体性质的地幔流体交代作用的一种微观表现。     

微细浸染型金矿含矿流体起源运移和成矿模式初探—— 以滇黔桂三角区金矿为例

本文以黔西南和挂西北微细浸染型金矿硅化与金矿化密切相关为依据,重点采用硅同位宋结合硅质阴极发光分析,再配合地质特征、成矿时代、系列元素、其它稳定同位东和流体包裹体地球化学研究并应用纳米成矿理论,探讨了该类型金矿含矿流体的起源、运移和成矿过程,认为原生含矿硅质流体可能主要直接起源于上地幔分异,其运移成矿过程表现为:沿深大断裂主通道由深至浅快速运移时,沿途进人次级容矿构造并向不同的有利于赋矿的地层渗透交代而成矿,初步揭示了有一定深度和埋廒封闭条件是该类型金矿成矿的有利条件,具有在深部形成大型和超大型矿床的潜在远景。     

Testing alternative ground water models using cross-validation and other methods

Many methods can be used to test alternative ground water models. Of concern in this work are methods able to (1) rank alternative models (also called model discrimination) and (2) identify observations important to parameter estimates and predictions (equivalent to the purpose served by some types of sensitivity analysis). Some of the measures investigated are computationally efficient; others are computationally demanding. The latter are generally needed to account for model nonlinearity. The efficient model discrimination methods investigated include the information criteria: the corrected Akaike information criterion, Bayesian information criterion, and generalized cross-validation. The efficient sensitivity analysis measures used are dimensionless scaled sensitivity (DSS), composite scaled sensitivity, and parameter correlation coefficient (PCC); the other statistics are DFBETAS, Cook's D, and observation-prediction statistic. Acronyms are explained in the introduction. Cross-validation (CV) is a computationally intensive nonlinear method that is used for both model discrimination and sensitivity analysis. The methods are tested using up to five alternative parsimoniously constructed models of the ground water system of the Maggia Valley in southern Switzerland. The alternative models differ in their representation of hydraulic conductivity. A new method for graphically representing CV and sensitivity analysis results for complex models is presented and used to evaluate the utility of the efficient statistics. The results indicate that for model selection, the information criteria produce similar results at much smaller computational cost than CV. For identifying important observations, the only obviously inferior linear measure is DSS; the poor performance was expected because DSS does not include the effects of parameter correlation and PCC reveals large parameter correlations.