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1.
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. We previously showed that O-linked triazolopyridazines can be potent inhibitors of c-Met. Herein, we report the discovery of a related series of N-linked triazolopyridazines which demonstrate nanomolar inhibition of c-Met kinase activity and display improved pharmacodynamic profiles. Specifically, the potent time-dependent inhibition of cytochrome P450 associated with the O-linked triazolopyridazines has been eliminated within this novel series of inhibitors. N-linked triazolopyridazine 24 exhibited favorable pharmacokinetics and displayed potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver PD model. Once-daily oral administration of 24 for 22 days showed significant tumor growth inhibition in an NIH-3T3/TPR-Met xenograft mouse efficacy model.  相似文献   

2.
In binding studies with rat brain membranes, 1,4-benzodiazepines containing a trifluoroethyl moeity at the 1-N position, including halazepam and quazepam, had significantly higher affinities for binding sites in cerebellum than in cortex. This selectivity for cerebellar sites is not a property of benzodiazepines without the trifluoroethyl moiety, but is similar to that seen with the triazolopyridazines. Since halazepam and quazepam, like the triazolopyridazines, have behavioral effects in animals at doses much lower than those that cause ataxia, it is tempting to attribute this separation of pharmacologic activities to differential activity at subpopulations of benzodiazepine receptors. Further work is necessary to clarify this possibility.  相似文献   

3.
Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (over)expression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders. In order to translate pre-clinical studies in cellular and mouse models to humans, differences and similarities of carboxylesterases between mice and human need to be elucidated. This review presents and discusses the research progress in structure and function of mouse and human carboxylesterases, and the role of these enzymes in lipid metabolism and metabolic disorders.  相似文献   

4.
The present study describes the fetal regions ethmoidalis and orbitotemporalis of the cranium of Galea musteloides and Kerodon rupestris and compares them with Galea spixii and Cavia porcellus . The fetal crania of these representatives of the Caviinae were serially sectioned and 3D plate reconstructions were built. For a broader scope, serially sectioned heads of the caviomorph taxa Hydrochaeris hydrochaeris and Dasyprocta leporina were also examined. The ethmoidal and orbitotemporal regions of the cranium provides characters that are pertinent to the discussion of systematics of the Caviinae. Nine cranial characters were identified as being significant and discussed phylogenetically. Taking the monophyly of the Cavioidea as given, two characters are autapomorphic for the genus Galea: the reduction of the crista semicircularis and the lacrimale forming the 'arco antorbitario' (Kraglievich 1930). Cavia is the sister group of Galea; synapomorphic characters are the extent of the processus palatinus medialis of the praemaxillare and the presence lamina pterygoidea of the alisphenoid. There were no apomorphic characters of the structural complexes examined that could support the Caviinae. The reduced and nonperforated alisphenoid is an autapomorphic feature of the Caviidae. The division of the nasoturbinale is evidence for a sistergroup relationship of the Hydrochaeridae and the Caviidae. Autapomorphic characters for the Cavioidea include the ventrolateral opening of the organon vomeronasale and the lateral prolongation of the lacrimale.  相似文献   

5.
The objective of this minireview is to examine how cometabolic biodegradation of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) might be affected by plant terpenes and lignins as natural substrates abundant in nature. The topics covered, hence, are environmental significance of PCBs and PAHs, nature and distribution of plant terpenes and lignin, structural and metaoblic similarities of the natural compounds to PCBs and PAHs, and possible roles of the natural substrates in inducing the biodegradative pathways of PCBs and PAHs.  相似文献   

6.
水稻胚与胚乳分化发育中的内源多胺   总被引:1,自引:0,他引:1  
稻胚发育过程中,其内源多胺以腐胺、亚精胺为主。在幼胚分化期,腐胺和亚精胺的含量很高;幼胚分化完成时,其含量急剧下降;直至分化后期才趋稳定。在胚及胚乳发育时期,还出现一种未知多胺X_(22),其含量除在胚分化完成时较少外,在胚发育的其他各期中,含量则一直很高。DNA和蛋白质含量的变化,从分化期开始递增直至物质积累成熟期,其趋势均相同。多胺可能参与胚与胚乳中核酸和蛋白质合成的调节。  相似文献   

7.
Phenotypic traits are often integrated into evolutionary modules: sets of organismal parts that evolve together. In social insect colonies, the concepts of integration and modularity apply to sets of traits both within and among functionally and phenotypically differentiated castes. On macroevolutionary timescales, patterns of integration and modularity within and across castes can be clues to the selective and ecological factors shaping their evolution and diversification. We develop a set of hypotheses describing contrasting patterns of worker integration and apply this framework in a broad (246 species) comparative analysis of major and minor worker evolution in the hyperdiverse ant genus Pheidole. Using geometric morphometrics in a phylogenetic framework, we inferred fast and tightly integrated evolution of mesosoma shape between major and minor workers, but slower and more independent evolution of head shape between the two worker castes. Thus, Pheidole workers are evolving as a mixture of intracaste and intercaste integration and rate heterogeneity. The decoupling of homologous traits across worker castes may represent an important process facilitating the rise of social complexity.  相似文献   

8.
张淑梅  李微  李丁男 《生物多样性》2022,30(6):22038-192
为给辽宁植物多样性保护提供本底数据, 更准确地评价植物濒危及保护等级, 以及更好地给农学、林学、生态学、系统学等研究提供可靠的基础性数据, 本文首次将几代人在辽宁境内发现的高等植物进行汇总、编目, 包括苔藓植物和维管束植物。苔藓植物根据正式发表的文献和中国科学院沈阳应用生态研究所东北生物标本馆(IFP)馆藏采自辽宁省全域的苔藓植物标本编制。维管束植物主要根据5个方面的信息整理: 作者多年野外调查的一手资料、文献、同行交流、公众提供信息、标本等。编目内容包括辽宁省高等植物总名录、辽宁省栽培植物名录、辽宁省外来植物名录、辽宁省仅有栽培植物的科属目录、辽宁省仅有外来植物的科属目录; 编目中涉及的物种均有科属地位、中文名、拉丁名、生境、产地(县级), 总名录中附有每个物种的信息凭证, 包括标本信息、文献信息或照片依据。本编目共计收录植物254科1,176属3,241种73亚种447变种119变型。其中, 苔藓植物为辽宁地区首次披露名录信息, 计83科205属491种4亚种7变种(含藓类52科156属373种1亚种5变种, 苔类29科46属114种3亚种2变种, 角苔类2科3属4种)。维管束植物虽非首次披露名录信息, 但与以往发布的维管束植物名录相比, 本次收录的种类数最多, 计171科971属2,750种69亚种440变种119变型(含石松类植物2科3属13种, 蕨类植物17科39属83种2亚种7变种, 裸子植物5科19属47种1亚种13变种2变型, 被子植物147科910属2,607种66亚种420变种117变型)。经统计, 辽宁省所有苔藓植物均为本土野生植物。维管束植物中, 野生植物计149科741属2,077种62亚种378变种93变型(含石松类植物2科3属13种, 蕨类植物17科39属83种2亚种7变种, 裸子植物4科8属12种6变种1变型, 被子植物145科133属1,969种60亚种365变种92变型), 栽培植物计104科390属673种7亚种62变种26变型(含裸子植物5科17属35种1亚种7变种1变型, 被子植物99科373属638种6亚种55变种25变型); 本土植物计158科796属2,235种65亚种421变种116变型(含石松类植物2科3属13种, 蕨类植物17科39属83种2亚种7变种, 裸子植物5科14属29种12变种2变型, 被子植物134科740属2,110种63亚种402变种114变型), 外来植物计88科316属515种4亚种19变种3变型(含裸子植物3科10属18种1亚种1变种, 被子植物85科306属497种3亚种18变种3变型)。本编目仅是辽宁省高等植物的阶段性汇总, 尚需要根据野外工作的拓展和研究工作的深入不断完善。  相似文献   

9.
Many recent developments in European marine and estuarine science have been against the demands of European Union legislation. The implementation of certain statutes, the role of scientists and the nature of the data required are discussed using examples from the UK, the Netherlands and Portugal. This includes the implementation of the EU Directives on Urban Waste-water Treatment, the control of Nitrates, the designation of Species and Habitats, the control of Dangerous Substances, the statutory requirement for Environmental Impact Assessments and the recently proposed Water Framework Directive. For these, the integration of physical, chemical and biological monitoring and investigation is discussed in relation to the science dictated by the legislative and administrative requirements. Each of these Directives requires the development of generic guidelines and protocols for implementation and the use of national enabling legislation. This indicates that, in several cases, the science should concentrate on monitoring and assessment in a well-structured and quality-controlled manner. The paper concludes by summarising developments based on similarities in the implementation of present and proposed Directives across Europe.  相似文献   

10.
An overview of the present status of the use of artificial insemination (AI) in South American camelids and wild equids is offered. Technical aspects of semen collection, dilution and cryopreservation have limited the development and use of AI in camelid and equid species. To-date, efficiency is low but progress has been made and viable offspring have been produced through the use of AI in domestic South American camelids using both fresh and frozen semen. The origin, composition, and function of the viscous component of camelid seminal plasma remain a mystery and an obvious area for future research. A better understanding of the normal constituents of seminal plasma will enable the rational design of semen extenders suitable for camelids. Post-thaw sperm viability is very low, and studies are needed to address questions of optimal freezing and thawing procedures as well as the insemination dose. The basis for differences in reported pregnancy rates with sexed and frozen semen in domestic equids, and the ultimate success of AI in wild equids will require continued research into the "stallion effect", extenders and cryoprotectants, optimal volume and number of spermatozoa, temperatures during handling, processing an transport, and insemination techniques. In both camelids and equids, research on domestic species under controlled conditions provides and excellent opportunity to develop effective semen handling techniques for application in wild and endangered species of the respective families.  相似文献   

11.
The viral, bacterial, fungal and nematode pathogens of arthropod pests of apple and pear in northern and central Europe and their use as biocontrol agents are reviewed. Baculoviruses are important viral pathogens of several lepidopterous pests of apple and pear but other viral pathogens have not been investigated in depth and are little known. The granuloviruses of codling moth, Cydia pomonella (CpGV), and to a lesser extent, of the summer fruit tortrix moth, Adoxophyes orana (AoGV), have been researched extensively and are exploited as biological control agents. Commercial development and use has been limited because of their high costs, slow action, short persistence and specificity relative to broad-spectrum pesticides. The widespread development of strains of codling moth multi-resistant to insecticides and the desire to reduce dependence on pesticides have improved the commercial prospects of CpGV and use is likely to increase. The development of a genetically improved egt-strain of CpGV (lacking the ecdysteroid-UDP glucosyl transferase gene) in the UK is a significant breakthrough, though commercialization in the UK may be difficult due to adverse public attitudes to the release of genetically-modified microorganisms. Future research and development approaches include further genetic manipulation of CpGV and AoGV to improve potency, speed of kill and/or persistence, improvement of formulation (to reduce UV light sensitivity) and development of cheaper mass production techniques and possibly in vitro production. A systematic search for baculoviruses and other viruses of apple and pear pests is likely to reveal important new opportunities. The most important bacterial pathogen used as a biological control agent is Bacillus thuringiensis (Bt). However, Bt products currently available have limited effectiveness against many orchard pests due to the pests' cryptic life habits. The HD-1 Bt strain has been investigated and used extensively for control of leaf-rolling tortricid larvae and is widely used, but efficacy is moderate. Advances in biotechnology and genetic engineering provide opportunity for development of Bt strains designed specifically to control orchard pests, but this has not yet been done for commercial reasons. Other research approaches include the evaluation of new Bt products developed for other markets worldwide and the bioassay of strains from Bt collections against specific apple or pear pests. Entomopathogenic fungi provide good opportunity for development as biological control agents of apple and pear pests. The main factor limiting their effectiveness is the requirement for high humidities and moderate temperatures for spore germination and development. For foliar pests, a useful starting point for research might be the control of sucking pests which excrete honeydew (e.g. Cacopsylla sp. or aphids) or those that inhabit protected microenvironments (e.g. Dasineura sp.). Key areas for research are improved formulation, the selection of low temperature-active strains, field evaluation and avoiding possible adverse effects of fungicides. An alternative approach is to examine the exploitation of entomopathogenic fungi in soil, to which many species of entomopathogenic fungi are adapted ecologically. Apple and pear orchards provide long-term stable habitats where populations of entomopathogenic fungi in soil are likely to be large. There are few important soil pests of apple or pear. However, many species spend part of their life in soil, mainly to pupate or overwinter, where they may be targeted by fungal entomopathogenic biocontrol agents. Entomopathogenic nematodes have many attributes which favour them as biological control agents. However, their requirement for surface moisture for survival and movement means there are only limited prospects for using them as biological control agents for foliar pests. As with entomopathogenic fungi, there are better prospects for control of pests that occur in soil. Microbial pathogens and entomopathogenic nematodes are important components of the natural enemy complex of apple and pear orchards and more effort needs to be devoted to fostering them and exploiting them as biocontrol agents in sustainable, biologically-based Integrated Pest Management programmes. They can in many cases be mass produced at low cost by bulk fermentation processes and applied as sprays (as 'biopesticides') and are, at least potentially, ideal biological control agents for many apple or pear pests. Important general characteristics are their comparative environmental and human safety, compatibility with other control strategies in Integrated Pest Management programmes and reproductive capacity. They tend to be effective in a narrower range of environmental conditions than pesticides, but there is considerable potential to improve their effectiveness by improved formulation, strain selection and genetic manipulation. They are often host-specific and thus, offer restricted marketing opportunities, which is a significant barrier to development and commercialisation. Registration procedures and associated fees for microbial agents are a further significant barrier. Such requirements do not apply currently to nematodes.  相似文献   

12.
The occurrence and properties of plant aminotransferases are considered in relation to the known characteristics of corresponding animal and bacterial aminotransferases. Development of aminotransferase systems during seed germination and plant development is examined and changes in the activity of various systems are discussed in relation to environmental factors and endogenous hormone changes. Purification and substrate specificity of various plant aminotransferases are considered and the evidence for substrate multispecificity shown by certain enzymes is related to similar findings with some animal and bacterial aminotransferases. The physical and kinetic properties of plant aminotransferases such as their molecular weight, sedimentation coefficient, subunit composition, pyridoxal phosphate requirement, effect of pH and cations on activity, and their mechanism of action are reviewed and compared to similar observations from animal and bacterial aminotransferases. Finally, the intracellular location and functions of plant aminotransferases and their isoenzyme composition are discussed and compared to those of corresponding animal enzymes.  相似文献   

13.
Cdc42 and Rac1 Rho family GTPases, and their interacting protein IQGAP1 are the key regulators of cell polarity. We examined the role of Cdc42 and IQGAP1 in establishing the polarity of mouse oocyte and regulation of meiotic and mitotic divisions. We showed that Cdc42 was localized on the microtubules of meiotic and mitotic spindle and in the cortex of mouse oocytes and cleaving embryos. IQGAP1 was present in the cytoplasm and cortex of growing and fully-grown oocytes. During maturation it disappeared from the cortex and during meiotic and mitotic cytokinesis it concentrated in the contractile ring. Toxin B inhibition of the binding activity of Cdc42 changed the localization of IQGAP1, inhibited emission of the first polar body, and caused disappearance of the cortical actin without affecting the migration of meiotic spindle. This indicates, that in maturing oocytes accumulation of cortical actin is not indispensable for spindle migration. In zygotes treated with toxin B actin cytoskeleton was rearranged and the first and/or subsequent cytokinesis were inhibited. Our results indicate that Cdc42 acts upstream of IQGAP1 and is involved in regulation of cytokinesis in mouse oocytes and cleaving embryos, rather than in establishing the polarity of the oocyte.  相似文献   

14.
以高效液相色谱技术检测在北京和内蒙古种植的供试材料Harosoy近等基因系的低聚糖及其组分含量,考查Harosoy近等基因系的低聚糖含量的变异和不同地点材料的低聚糖及其组分含量相互间的相关性,低聚糖及其组分含量分别与蛋白质、脂肪含量间的相关性。研究结果表明,内蒙古种植材料低聚糖含量的平均值均高于北京种植的材料,说明内蒙古的条件有利于大豆的低聚糖形成和贮存。北京和内蒙古的材料蔗糖含量分布范围分别是3.3%~6.5%、3.9%~6.9%,棉籽糖分布范围分别是0.6%~1.4%、0.7%~1.1%,水苏糖分布范围分别是2.7%~3.7%、2.8%~3.8%,大豆低聚糖分布范围分别是6.9%~10.9%、7.8%~11.3%。同时发现,两地种植材料的低聚糖含量间和蔗糖含量间均具有显著负相关性,蔗糖含量间r=-0.7810,低聚糖含量间r=-0.7355;低聚糖及其组分含量与蛋白质、脂肪含量间均无相关性(P0.05)。还发现了低聚糖及其组分含量在两地稳定表达的材料共10个。  相似文献   

15.
The structural state of two major nucleolar proteins, UBF and B23/nucleophosmin (both monomeric and oligomeric forms), was for the first time established in HeLa cells treated with apoptosis inducers: tumor necrosis factor (TNF-alpha), emetine, and their combination. The treatment of the cells with either TNF-alpha or emetine did not induce apoptosis and affect the state of UBF and nucleophosmin (both monomers and oligomers). Apoptosis was rather pronounced only if HeLa cells were treated with a mixture of TNF-alpha and emetine. States of the UBF and B23 proteins were analyzed in samples containing 25, 45, and 100% of cells with apoptotic nuclei. It was shown by immunoblotting that TNF-alpha-induced apoptosis of HeLa cells was associated with proteolysis of UBF and production of a 76-kD fragment, the content of which increased in correlation with the fraction of apoptotically changed cells. The N- and C-terminal amino acid sequences of UBF and its 76-kD fragment were characterized, and the site of the apoptosis-induced specific proteolysis was identified. As differentiated from UBF, protein B23 did not undergo proteolytic degradation during the TNF-alpha-induced apoptosis of HeLa cells and its content was unchanged even in the cell fraction with fragmentation of virtually all nuclei. However, the ratio between the monomeric and oligomeric states of B23 protein was changed in apoptotic cells, and apoptosis-specific forms of nucleophosmin were detected.  相似文献   

16.
Both heparanase and syndecan-1 are known to be present and active in disease pathobiology. An important feature of syndecan-1 related to its role in pathologies is that it can be shed from the surface of cells as an intact ectodomain composed of the extracellular core protein and attached heparan sulfate and chondroitin sulfate chains. Shed syndecan-1 remains functional and impacts cell behavior both locally and distally from its cell of origin. Shedding of syndecan-1 is initiated by a variety of stimuli and accomplished predominantly by the action of matrix metalloproteinases. The accessibility of these proteases to the core protein of syndecan-1 is enhanced, and shedding facilitated, when the heparan sulfate chains of syndecan-1 have been shortened by the enzymatic activity of heparanase. Interestingly, heparanase also enhances shedding by upregulating the expression of matrix metalloproteinases. Recent studies have revealed that heparanase-induced syndecan-1 shedding contributes to the pathogenesis and progression of cancer and viral infection, as well as other septic and non-septic inflammatory states. This review discusses the heparanase/shed syndecan-1 axis in disease pathogenesis and progression, the potential of targeting this axis therapeutically, and the possibility that this axis is widespread and of influence in many diseases.  相似文献   

17.
Research on the influence of sea level variations on the benthic faunas have been carried out in the Upper Ordovician of Sardinia. Study of the depositional facies and sequence analysis of the upper part (Lower Ashgill) of the Portixeddu Formation led to the identification of the sedimentary environments. Cystoids and crinoids are associated to bryozoans and brachiopods in most levels. The numerical analysis of associations and megaguilds shows that crinoids and cystoids have a higher frequency in the proximal and median facies of the upper offshore. The columnal association characterized by Conspectocrinus celticus and the coronoid Mespilocystites tregarvanicus has been discovered in the upper part of the formation. This material and complementary samples from Upper Ordovician of Sardinia and Kabylia (Algeria) bring additional data on the systematic and show the wide distribution of this fauna outside of the Ibero-armorican domain. The distribution of this echinoderm association supports a palaeogeographical position of the Ibero-armorican domain and Sardinia within the north gondwanan margin during the Lower Palaeozoic.  相似文献   

18.
The paper reviews the main findings of rocky shore and subtidal nearshore experimental marine ecology (EME) in cold and temperate marine ecosystems during the past four decades. It analyzes the role of EME in coastal management and conservation. The historical development of strategies for managing single or multispecies fisheries are reviewed. The published results show over-exploitation and depletion of more than 60% of the fish stocks and a lack of connection between the management of fisheries and results derived from experimental marine ecology. This is mainly due to: (a) the different temporal and spatial scale at which most marine ecologists and fishery managers operate; (b) the lack of long-term fishery monitoring and adaptive techniques for management; and (c) limitations in the design of experiments on fisheries. Large-scale oceanic perturbations, due to combinations of excessive resource exploitation and environmental variability coupled with present trends in management approaches are discussed. Modern approaches and tools for management of fisheries, such as Adaptive Management (AM), Territorial User Rights in Fisheries (TURFs), Individual Transferrable Quotas and Non-Transferrable Quotas (ITQs, INTQs) are discussed in the context of small-scale fisheries and EME. Published views on limits of applied ecological research with regards to management of fisheries are discussed. Linkages between EME, marine conservation and the establishment of Marine Protected Areas (MPAs) and experimental exclusions of humans are highlighted. Results derived from MPAs, such as: (a) species or community trophic cascades, and (b) the role of key-stone species and species interaction strengths, are discussed. It is concluded that the role of EME in conservation has been greater than has been the case in management of fisheries. The potential to link EME, conservation and the management of fisheries is exemplified through the proposed establishment in Chile of a connected network of Scientific Reserves, MPAs and TURFs sites. The final conclusion is that to cross-fertilize EME, conservation and management, there are three main challenges: (1) to end the traditional view of approaching the management of fisheries and marine conservation as contradictory/antagonizing issues; (2) to improve communications between experimental marine ecology and the management of fisheries through the implementation of experimentation and adaptive management; (3) to improve linkages between marine conservation, the management of fisheries and social sciences.  相似文献   

19.
Spirits are part of everyday life in the Kingdom of Tonga. This study explores beliefs about the supernatural by analyzing discourse on spirits and death and by examining two examples of contemporary cultural practice related to spirits and death. The anthropological concepts of the body and its cultural construction and of thirdspace as a landscape of the Tongan islands that emerges out of the physical and the perceived provide the framework for this investigation. Research findings suggest that spirits participate in the natural order of Tongan society and thus serve to help maintain cultural identity in the face of uncertain social change and a popular but contested prodemocracy movement. Spirits also function as a system of representation, mirroring an image of an ideal self, something that is continually under negotiation. Encounters between spirits of ancestors and their living descendants suggest an uneasy acceptance of death and a sense of irony about its inevitability.  相似文献   

20.
The leaf anatomy of the rhizomatous Iris species with ensiform leaves and the related genera Pardanthopsis and Belamcanda is described. Their isobilateral leaves may or may not have a pseudo-dorsiventral structure. Variable characters of their leaf blades include: outline in transverse section, height and shape of papillae, form and structure of stomata, transverse section outline of marginal fibre strands and sclerenchy matous inner bundle sheath at phloem and xylem poles, forms of mesophyll arrangement, mesophyll structure and air canals, vascular bundle arrangement and the detailed structure of the larger vascular bundles, distribution of tannin, size and distribution of crystals. The taxonomic and ecological significance of these characters has been evaluated.
The anatomical characteristics of 25 supraspecific taxa in three genera are presented and compared in tables. The relationships and evolutionary position of these taxa are discussed. Each of the three subgroups within Iris appears to be correlated with a syndrome of anatomical characters. Some species currently of uncertain taxonomic position are discussed, and their classification based on anatomical data is suggested.
Some characters related to xeromorphy or helomorphy are mentioned.  相似文献   

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