基因芯片筛选氯化汞对大鼠脑神经毒性差异表达基因

为了筛选汞神经毒性差异表达基因和探讨汞神经毒性分子机制,采用基因芯片技术,研究了大鼠皮下注射0.5mg/kg的HgCl₂ 1h后脑中基因表达的变化.结果表明,基因表达谱中差异表达基因共有742条,上调基因562条,下调基因180条.生物信息学分析表明,差异表达基因中有免疫应答及解毒作用相关基因、遗传信息传递与表达相关基因、细胞信号传导基因、神经传导基因、细胞增殖与分化基因、细胞调亡等多种基因.分析结果提示这些基因的差异表达可能与汞神经毒性有关.利用基因芯片技术筛选相关基因,为深入阐明汞神经毒性的作用机制提供了新思路.     

Physik der biologischen Gestaltbildung

In each generation cycle of a higher organism, a complex structure is formed under the instruction of the genes. In this process morphogenetic fields (probably spatial concentration patterns of substances) are involved which elicit cell responses giving rise to visible pattern and form. Autocatalytic short-range activation in conjunction with long-range (“lateral”) inhibition is capable of generating striking concentration patterns starting from near-uniform distributions. No features unusual in molecular biology are required, and self-regulatory properties observed experimentally in biological development can be accounted for. Cell responses to morphogenetic fields can include cell differentiation and the generation of bending moments, curvature and form in cell sheets giving rise to defined forms in organs and organisms. It appears that biological pattern formation is explicable on the basis of known physical laws and processes.     

Anpassung des Zellstoffwechsels an Umweltänderungen

In the living cell transfer ribonucleic acids (tRNAs) serve for the transfer of information from genes to proteins. In this article evidence will be presented showing that changes of particular tRNA modifications cause alterations in gene expression, when an organism is exposed to a metabolic stress, e.g. limitation of oxygen or nutrients. tRNA modifications seem to be important to adapt cells to environmental changes. These mechanisms of adaptation are considered to have developed as survival strategies in microorganisms especially when oxygen accumulated in the atmosphere.     

The immunoglobulin-like genetic predetermination of the brain: the protocadherins, blueprint of the neuronal network

The morphogenesis of the brain is governed by synaptogenesis. Synaptogenesis in turn is determined by cell adhesion molecules, which bridge the synaptic cleft and, by homophilic contact, decide which neurons are connected and which are not. Because of their enormous diversification in specificities, protocadherins (pcdh!, pcdh#, pcdh%), a new class of cadherins, play a decisive role. Surprisingly, the genetic control of the protocadherins is very similar to that of the immunoglobulins. There are three sets of variable (V) genes followed by a corresponding constant (C) gene. Applying the rules of the immunoglobulin genes to the protocadherin genes leads, despite of this similarity, to quite different results in the central nervous system. The lymphocyte expresses one single receptor molecule specifically directed against an outside stimulus. In contrast, there are three specific recognition sites in each neuron, each expressing a different protocadherin. In this way, 4,950 different neurons arising from one stem cell form a neuronal network, in which homophilic contacts can be formed in 52 layers, permitting an enormous number of different connections and restraints between neurons. This network is one module of the central computer of the brain. Since the V-genes are generated during evolution and V-gene translocation during embryogenesis, outside stimuli have no influence on this network. The network is an inborn property of the protocadherin genes. Every circuit produced, as well as learning and memory, has to be based on this genetically predetermined network. This network is so universal that it can cope with everything, even the unexpected. In this respect the neuronal network resembles the recognition sites of the immunoglobulins.     

PFOS暴露对肺癌细胞中信号通路的影响

为探讨全氟辛烷磺酸盐（PFOS）产生肺毒性的分子机制,采用细胞计数试剂盒（CCK-8）方法测定不同浓度PFOS对A549细胞活性的影响,并用二代测序方法测定PFOS暴露对A549细胞中miRNAs表达的影响,预测异常表达miRNAs的靶基因.通过生物信息学分析推断靶基因参与的信号通路及潜在的生物学功能.结果显示,低浓度PFOS（<00μmol/L）促进A549细胞增殖,高浓度PFOS抑制细胞增殖.暴露于300μmol/L PFOS中24h的A549细胞中108个miRNAs表达量显著上调,63个miRNAs表达量显著下调.差异表达miRNAs通过Ras、Rap1、HIF-1、ErbB和VEGF等信号通路参与细胞增殖、代谢和发育等生物学过程.这表明PFOS可通过影响细胞增殖和诱发炎症反应对肺造成威胁.     

Gen-Struktur und Gen-Expression

In the chicken oviduct the synthesis of the egg-white proteins ovalbumin, conalbumin, ovomucoid and lysozyme is controlled by the female sex steroids. The steroid-controlled rate of synthesis of these proteins is closely correlated to the cellular concentration of the egg-white protein mRNAs. The accumulation of these mRNAs is achieved by a drecreased rate of degradation and an increased rate of synthesis. To understand the molecular mechanism that regulates the expression of this group of genes we have isolated the lysozyme and ovomucoid gene by gene-cloning. The structure and expression of the lysozyme gene has been studied.     

生态敏感性评价在生态文明建设中的运用研究——以四川省蓬安县为例

以四川省蓬安县为例,基于GIS空间分析技术,结合蓬安当地实际,选取水源涵养、土壤保持能力和生物多样性进行生态敏感性评价,获得蓬安县区域敏感性现状图,并以此为基础构建生态安全格局,该格局注重区域的内在机理与周围的相对联系,保证各生态环境功能区成为具有各自特点、功能和生命活力而又彼此联系的有机体,为其生态文明建设过程中重点领域和重点工程设计规划提供基础支撑,阐明了生态敏感性评价在生态文明建设中的运用,为县级生态文明建设规划做出了贡献.     

Role of RNA interference in plant improvement

Research to alter crops for their better performance involving modern technology is underway in numerous plants, and achievements in transgenic plants are impacting crop improvements in unparalleled ways. Striking progress has been made using genetic engineering technology over the past two decades in manipulating genes from diverse and exotic sources, and inserting them into crop plants for inducing desirable characteristics. RNA interference (RNAi) has recently been identified as a natural mechanism for regulation of gene expression in all higher organisms from plants to humans and promises greater accuracy and precision to plant improvement. The expression of any gene can be down-regulated in a highly explicit manner exclusive of affecting the expression of any other gene by using RNAi technologies. Additional research in this field has been focused on a number of other areas including microRNAs, hairpin RNA, and promoter methylation. Manipulating new RNAi pathways, which generate small RNA molecules to amend gene expression in crops, can produce new quality traits and having better potentiality of protection against abiotic and biotic stresses. Nutritional improvement, change in morphology, or enhanced secondary metabolite synthesis are some of the other advantages of RNAi technology. In addition to its roles in regulating gene expression, RNAi is also used as a natural defense mechanism against molecular parasites such as jumping genes and viral genetic elements that affect genome stability. Even though much advancement has been made on the field of RNAi over the preceding few years, the full prospective of RNAi for crop improvement remains to be fully realized. The intricacy of RNAi pathway, the molecular machineries, and how it relates to plant development are still to be explained.     

环境内分泌干扰物促进乳腺细胞增殖的分子机制研究进展

乳腺癌是女性中常见的癌症,EDCs（environmental endocrine disrupting chemicals,环境内分泌干扰物）具有雌激素活性,能促进乳腺细胞的增殖,明确EDCs在乳腺癌细胞增殖中的作用和机制,有助于乳腺癌的预防.在归纳整理国内外相关研究基础上,总结了EDCs通过激活雌激素受体信号通路、抑制细胞凋亡和改变细胞周期等方面促进乳腺细胞的增殖,并对其分子机制进行了全面综述.EDCs促进乳腺细胞增殖的分子机制有:①EDCs通过与雌激素核受体（nERs）结合形成二聚体,改变受体构象,并结合到靶基因雌激素响应元件（ERE）上,进而调控增殖相关靶基因转录和蛋白表达;②EDCs也可通过与雌激素膜受体（mERs）结合,激活快速非基因组信号通路,改变靶蛋白活性或靶基因表达;③EDCs也可通过上调凋亡抑制蛋白Bcl-2和Bcl-xL的表达,抑制细胞凋亡;④EDCs还可通过上调细胞周期蛋白（cyclin）表达、提高周期依赖性蛋白激酶（CDKs）活性,加快细胞周期;⑤EDCs通过基因组、非基因组信号途径的交互,上调cyclin D和c-Myc表达,再通过CDK磷酸化细胞周期调节因子Rb蛋白,释放转录因子E2Fs,加速细胞从G₁期向S期的转变,促进细胞增殖.建议今后从与内源激素交互、影响雌激素E₂合成以及低剂量联合作用3个方面来探讨EDCs对乳腺细胞的增殖机制,以期为乳腺致癌物的筛查、乳腺癌预防和治疗以及乳腺细胞增殖机制的深入研究提供参考.      

Prenatal testing for imprinting disorders: A laboratory perspective

Imprinting Disorders (ImpDis) are a group of congenital syndromes associated with up to four different types of molecular disturbances affecting the monoallelic and parent-of-origin specific expression of genomically imprinted genes. Though each ImpDis is characterized by aberrations at a distinct genetic site and a specific set of postnatal clinical signs, there is a broad overlap between several of them. In particular, the prenatal features of ImpDis are non-specific. Therefore, the decision on the appropriate molecular testing strategy is difficult. A further molecular characteristic of ImpDis is (epi)genetic mosaicism, which makes prenatal testing for ImpDis challenging. Accordingly, sampling and diagnostic workup has to consider the methodological limitations. Furthermore, the prediction of the clinical outcome of a pregnancy can be difficult. False-negative results can occur, and therefore fetal imaging should be the diagnostic tool on which decisions on the management of the pregnancy should be based. In summary, the decision for molecular prenatal testing for ImpDis should be based on close exchanges between clinicians, geneticists, and the families before the initiation of the test. These discussions should weigh the chances and challenges of the prenatal test, with focus on the need of the family.     

The evolutionary processes of mitochondrial and chloroplast genomes differ from those of nuclear genomes

This paper first introduces our present knowledge of the origin of mitochondria and chloroplasts, and the organization and inheritance patterns of their genomes, and then carries on to review the evolutionary processes influencing mitochondrial and chloroplast genomes. The differences in evolutionary phenomena between the nuclear and cytoplasmic genomes are highlighted. It is emphasized that varying inheritance patterns and copy numbers among different types of genomes, and the potential advantage achieved through the transfer of many cytoplasmic genes to the nucleus, have important implications for the evolution of nuclear, mitochondrial and chloroplast genomes. Cytoplasmic genes transferred to the nucleus have joined the more strictly controlled genetic system of the nuclear genome, including also sexual recombination, while genes retained within the cytoplasmic organelles can be involved in selection and drift processes both within and among individuals. Within-individual processes can be either intra- or intercellular. In the case of heteroplasmy, which is attributed to mutations or biparental inheritance, within-individual selection on cytoplasmic DNA may provide a mechanism by which the organism can adapt rapidly. The inheritance of cytoplasmic genomes is not universally maternal. The presence of a range of inheritance patterns indicates that different strategies have been adopted by different organisms. On the other hand, the variability occasionally observed in the inheritance mechanisms of cytoplasmic genomes reduces heritability and increases environmental components in phenotypic features and, consequently, decreases the potential for adaptive evolution.     

Modulation of the DNA repair system and ATR-p53 mediated apoptosis is relevant for tributyltininduced genotoxic effects in human hepatoma G2 cells

The toxic effects of tributyltin (TBT) have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1-4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly (ADP-ribose) polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related (ATR) protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes migration ability of primary cultured rat astrocytes via aryl hydrocarbon receptor

Emerging evidence showed that 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) could induce expression of certain reactivation-associated genes in astrocytes, however, the consequent cellular effects and molecular mechanisms are still unclear. During the process of astrocyte reactivation, migration is a critical cellular event. In the present study, we employed wound-healing assay and Transwell® motility assay to explore the effects of TCDD on cell migration in primary cultured rat cortical astrocytes. We found that upon TCDD treatments at relative low concentrations (10^? 10 and/or 10^? 9?mol/L), the ability of primary astrocytes to migrate horizontally and vertically was promoted. In line with this cellular effect, the mRNA expression of two pro-migratory genes, including cell division cycle 42 (CDC42) and matrix metalloproteinase 2 (MMP2) was induced by TCDD treatment. Dioxin exerts its toxic effects mainly through aryl hydrocarbon receptor (AhR) pathway. So the role of AhR pathway in the pro-migratory effects of TCDD was examined using an AhR antagonist, CH223191. We found that application of CH223191 significantly reversed the pro-migratory effects of TCDD. Interestingly, the basal ability of horizontal migration as well as basal levels of CDC42 and MMP2 expression were dramatically reduced suggesting a possible physiological role of AhR in maintaining the endogenous migration ability of the primary astrocytes. These findings support the notion that dioxin promotes astrocyte reactivation at molecular and cellular levels.     

Insect damage influences heat and water stress resistance gene expression in field-grown popcorn: implications in developing crop varieties adapted to climate change

Warming climatic conditions can pose problems for crop production in many parts of the world, but detailed information on the expression of heat and drought stress resistance genes of potentially affected crop plants is lacking. This information is important to have in order to most efficiently guide the breeding of crops that are adapted to new climatic conditions. A maize (Zea mays) gene microarray, a method used worldwide to evaluate the expression of tens of thousands of genes at once, was used to investigate changes in expression of genes involved in resistance to heat and water stress in milk stage popcorn kernels from undamaged and insect-damaged ears. Popcorn is a form of maize that is more susceptible to heat and drought stress due to its smaller root system. In years of heat and drought stress, expression of many heat shock- and senescence-related proteins increased compared to the year when weather was closer to average conditions, but the expression of many genes related to drought stress resistance decreased in years of weather stress. A different complex of heat shock protein and water stress resistance protein genes had higher expression in kernels from undamaged compared to insect-damaged ears in years of heat and drought stress. These results indicate that the interaction of biotic components, such as insects, are important to consider in developing crop lines with adaptation to stress as this will help identify additional genes and their regulatory components involved in heat and drought stress resistance that might otherwise be overlooked, and will likely be an important strategy for the most effective development of climate stress-tolerant crops globally.     

Molekulare Zellbiologie der Hitzestrefßantwort

The coordinate induction of distinct genes by heat stress and a considerable number of chemical stressors depend on a common regulatory element in the promoter found in front of related genes of all eukaryotic systems. This element can be used for the construction of universal heat stress expression cassettes. The increasingly broad interest in the heat stress response and the genes involved also results from medical aspects, e.g., the potential application of hyperthermia in cancer therapy, the intricate connections of stress proteins and genes with malignant transformation, and the remarkable role of heat stress proteins as dominant antigens of infectious and autoimmune diseases.     

Das Pinealorgan der Wirbeltiere: ein Modell für Untersuchungen von Rezeptor-und Effektormechanismen in neuronalen Systemen

Cell and molecular biological investigations have greatly contributed to our understanding of receptor and effector mechanisms in sensory, neuronal, and endocrine cells. A fascinating aspect of this line of research is how such mechanisms have evolved and how they interact with each other. As shown in this contribution, the vertebrate pineal organ is an interesting model to study these problems, because it undergoes a conspicuous transformation during phylogeny, comprises two well-chraracterized receptor mechanisms (photoreception and adrenoreception), and acts upon its targets via neuronal and neuroendocrine signals.

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Herrn Professor Dr. Drs. h. c. A. Oksche zum 65. Geburtstag gewidnet     

Programmed cell death induced by modified clay in controlling Prorocentrum donghaiense bloom

Modified clay (MC), an effective material used for the emergency elimination of algal blooms, can rapidly reduce the biomass of harmful algal blooms (HABs) via flocculation. After that, MC can still control bloom population through indirect effects such as oxidative stress, which was initially proposed to be related to programmed cell death (PCD) at molecular level. To further study the MC induced cell death in residual bloom organisms, especially identifying PCD process, we studied the physiological state of the residual Prorocentrum donghaiense. The experimental results showed that flocculation changed the physiological state of the residual cells, as evidenced by growth inhibition and increased reactive oxygen species production. Moreover, this research provides biochemical and ultrastructural evidence showing that MC induces PCD in P. donghaiense. Nuclear changes were observed, and increased caspase-like activity, externalization of phosphatidylserine and DNA fragmentation were detected in MC-treated groups and quantified. And the mitochondrial apoptosis pathway was activated in both MC-treated groups. Besides, the features of MC-induced PCD in a unicellular organism were summarized and its concentration dependent manner was proved. All our preliminary results elucidate the mechanism through which MC can further control HABs by inducing PCD and suggest a promising application of PCD in bloom control.     

Chemical carcinogenesis — the price for DNA-repair?

This essay examines the possibility of merging the mutation theory of cancer with the hypothesis that cancer is a change in the state of the differentiation of cells. It is suggested that during normal development DNA rearrangements occur, concerning genes which code for differentiation specific cell communication proteins. These proteins are responsible for the proper functioning of growth control in a multicellular organism. DNA-damaging agents — mutagens — induce DNA repair enzymes, some of which may catalyse illegitimate genome rearrangements, thus leading to a change of the balance between growth and differentiation. A cell with a selective advantage may arise and become the origin of a tumor.