HIFs and tumors--causes and consequences

For most organisms oxygen is essential fo life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counter act possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an alpha- and a beta-subunit. HIF-1 alpha protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.     

Prenatal ages and stages-measures and errors

BACKGROUND: The confusing term "gestational age" is generally either not defined or is used for menstrual "age," postovulatory age, or postfertilizational age. The designation (post)menstrual weeks and/or days is very useful in obstetrics but, because prenatal age extends from fertilization to birth, menstrual "age" is a misnomer. The term "stage" has a specific morphological meaning in embryology and should not be used either for ages or for lengths. METHODS: Embryonic age is best assessed, when possible, from the 23 internationally recognized morphological stages. A morphological staging system is not available for the fetal period, and fetal age is assessed mainly from measurements. RESULTS: Among these, the unsatisfactory designation crown-rump length (CRL) should be replaced, in ultrasonic biometry as well as in embryology, by the greatest length (GL), exclusive of the lower limbs. These points are discussed in detail, and justification for the views expressed is provided. CONCLUSIONS: The continuing confusion concerning prenatal age is shown to be unnecessary once the ambiguous and superfluous term "gestational age" is abandoned.     

Astrocytes and Synaptosomes Transport and Metabolize Lactate and Acetate Differently

Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.     

Liquid chromatographic assay of phenothiazine, thioxanthene and butyrophenone neuroleptics and antihistamines in blood and plasma with conventional and radial compression columns and UV and electrochemical detection

An assay strategy for determining a wide range of phenothiazine, thioxanthene and butyrophenone neuroleptics and antihistamines both alone and in combination in blood and plasma is described. The general method employs liquid chromatography with both conventional and radial compression nitrile bonded columns. Detection is by ultraviolet absorption spectrophotometry or by amperometry depending on the concentrations to be measured. Ultraviolet absorption is suitable down to 10 ng/ml. Below this level amperometry is preferable. The various compounds are used as internal standards for each other. The lower limit of detection is approximately 0.1 ng ml⁻¹ with a 10-ml sample. The within-run coefficient of variation is a maximum of 7.3%.     

Phylogeny and taxonomy of Aspicilia and Megasporaceae

Phylogenetic analyses based on nuLSU and mtSSU indicate that Megasporaceae is monophyletic. Aspicilia species were distributed among three main well supported groups and one group with low support that included the type species; a division of the family into five genera is proposed. The old names Circinaria and Sagedia are reintroduced for groups not including A. cinerea, the type of Aspicilia. The monotypic Megaspora is closely related to Circinaria, while Lobothallia is the sister group of the other Megasporaceae genera. Aspicilia recedens and A. farinosa are transferred to Lobothallia. Species of the 'Sphaerothallia group' are nested in Circinaria. Aspilidea is not a member of Megasporaceae but seems to be more closely related to Ochrolechiaceae. Aspilidea myrinii is neotypified, and lectotypes are designated for Aspicilia gibbosa, A. leprosescens and Lecanora gibbosula.     

姜黄色素及其提制方法

来源于姜科姜黄属植物姜黄根茎的姜黄是国内外食品行业允许使用的重要天然色素之一,具有重要的开发利用价值。姜黄素的主要提取方法可分为有机溶剂提取法和水提取法;精制方法主要包括专一性溶剂法、酸碱法、酶水解法和柱层析法等。文中对各种方法进行了简要介绍和评述。     

Polarity and form regulation in development and reconstitution

In the literature, it is often assumed, for example with respect to Hydra, that several Turing systems coexist and it is also assumed that maintaining the polar profile, even when the system increases in size, is important for the polarity of the final phenotype. It is shown here that in reality there is only one Turing system, Child's system. To obtain a complete polar individual or organ, whether in reconstitution or development, it is essential that the complete succession of metabolic patterns occurs. Child's concepts of physiological dominance, subordination and isolation are interpreted in the light of Turing theory and in particular the Turing wavelength. It is emphasised, particularly by pointing to Child's metabolic patterns in coelenterates, both in development and in reconstitution, that it is the elongation that drives the succession polar metabolic pattern-->bipolar metabolic pattern, and this corresponds to the prediction of Turing theory supporting the thesis that Child's metabolic pattern is a Turing pattern. It is shown that if we assume that ATP is the Turing inhibitor then the many results of Child about the reduction of the scale of organisation with the decrease in the intensity of the energy metabolism correspond to the reduction of the Turing wavelength. The interplay between the Turing wavelength and the length of the form explains the conditions of reconstitution under which partial forms, wholes and form regulation are obtained. It is suggested that higher metabolism is responsible for both larger size and larger Turing wavelength thus securing form regulation. The results could be of importance in modern 'regenerative biology'. Heteromorphosis, i.e. animals with two heads (or two tails), one at each end, is explained by a bipolar Turing-Child metabolic pattern replacing a polar metabolic pattern. This can be brought about by chemical or by genetic means and indeed the prediction for Drosophila that the transition, wild type-->Bicaudal D, occurs because a polar Turing pattern is replaced by bipolar Turing pattern is confirmed, again if we accept that Child's metabolic pattern is the underlying Turing pattern. Child's experiments on Drosophila, including the requirement of critical length for metabolic polarity, are explained by Turing theory. Phenocopies and phenotypes are explained by the Turing-Child theory. It is shown that both Child's results about metabolic patterns and modern results for Hydra about gap junctions, 'endogeneous inhibitor' and gene expression, are correlated and explained by (cAMP, ATP) Turing theory. It is argued that the double-gradient hypothesis is incorrect in its original formulation and that it is Child's conception of succeeding metabolic patterns that is the correct one and that it corresponds to the prediction of the Turing theory.     

Multi-scale lines and edges in V1 and beyond: Brightness,object categorization and recognition,and consciousness

In this paper we present an improved model for line and edge detection in cortical area V1. This model is based on responses of simple and complex cells, and it is multi-scale with no free parameters. We illustrate the use of the multi-scale line/edge representation in different processes: visual reconstruction or brightness perception, automatic scale selection and object segregation. A two-level object categorization scenario is tested in which pre-categorization is based on coarse scales only and final categorization on coarse plus fine scales. We also present a multi-scale object and face recognition model. Processing schemes are discussed in the framework of a complete cortical architecture. The fact that brightness perception and object recognition may be based on the same symbolic image representation is an indication that the entire (visual) cortex is involved in consciousness.     

Mandibular Function and Biomechanical Stress and Scaling

Patterns of stress were analyzed in the mandibular symphysisof Macaca fascicularis using rosette strain gages. During jawopening, the mandibular symphysis is bent due to medial transversebending of the mandibular corpora. Levels of stress and strainare relatively low at this time, and the source of this stressis the medially-directed component of force from the lateralpterygoid muscles. During the power stroke of mastication, thesymphysis is maximally stressed. At this time the symphysisexperiences dorsoventral shear and bending due to lateral transversebending of the mandibular corpora, i.e., "wishboning." The dorsoventralshear is due to the vertical component of the balancingsideadductor muscle force; the "wishboning" is due to the laterally-directedcomponents of the bite and jaw adductor muscle forces. Unlikedorsoventral shear, "wishboning" results in considerable levelsof stress and strain, particularly along the most lingual aspectof the symphysis. The most effective way to counter this stressis to increase the thickness of the symphysis in the labio-lingualdirection. The stress analysis and an allometric analysis ofmandibular dimensions in female cercopithecine (Old World) monkeysindicates that allometric changes in the symphysis are readilyunderstood if the mandible is modelled as a curved beam. Withincreasing body size, symphyseal thickness in cercopithecinesmust increase in a positively allometric fashion so as to preventthe occurrence of dangerously high levels of stress along themost lingual aspect of the symphysis. This is because increasingbody size is associated with three factors thathave importantconsequences within the context of the biomechanics of curvedbeams: (1) jaw length is positively allometric to body size,(2) mandibular-arch width is negatively allometric to body size,and (3) there is a tendency to use relatively greater amountsof balancing-side jaw muscle force with increased body sizebecause of dietary changes and allometricconstraints on totaljaw muscle force.     

Synthesis and biological evaluation of cepharadiones A and B and related dioxoaporphines

Described herein is the first total synthesis and structural confirmation of cepharadione A, a naturally occurring DNA damaging agent. Also reported is the synthesis of cepharadione B, a closely related natural product, as well as the biological evaluation of both natural products. Finally, the preparation and biological evaluation of novel dioxoaporphine analogues is described.     

Selection, subdivision and extinction and recolonization

In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity N(e)s(e), which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations.     

The effects of legislation and policy in New Zealand and Australia on biosecurity and arthropod biological control research and development

The widespread and intensive application of biological control can create serious gaps between what may be naïve expectation versus reality. An extreme view is that there is a biological control solution for every problem. Similarly, there is the expectation that there are readily available and cheap biosecurity measures that, while having no effect on trade, work flawlessly. Such expectations can lead to two areas of difficulty. The first is that science is seen to have failed when biological control does not work as well as hoped for (and/or there are impacts on non-target species). The second is that people expect a huge amount from their biosecurity.Alongside this there has been the emergence of legislated—for precautionary principle—based expectation of technical certainty. This is particularly problematic when applied to complex ecological questions. Such circumstances have led to something of a disjunct between the expectations of legislators and what is required of the implementing agencies. This in turn has elicited difficulties in terms of what science is able to deliver for a reasonable/acceptable cost. Such cost is often borne by applicant groups, etc. It is aspects of the above situation that have contributed to the politicisation of biological control and biosecurity issues in New Zealand in the last 15 years.This contribution highlights some of the differences between legislation, policy and what science can deliver relating to biological control and biosecurity in New Zealand and Australia, and discusses some of the inconsistencies and impracticalities in their implementation with a focus on arthropod biological control examples.     

Ontogeny and phylogeny of endothermy and torpor in mammals and birds

Endothermic thermoregulation in small, altricial mammals and birds develops at about one third to half of adult size. The small size and consequently high heat loss in these young should result in more pronounced energetic challenges than in adults. Thus, employing torpor (a controlled reduction of metabolic rate and body temperature) during development would allow them to save energy. Although torpor during development in endotherms is likely to occur in many species, it has been documented in only a few. In small, altricial birds (4 orders) and marsupials (1 order), which are poikilothermic at hatching/birth, the development of competent endothermic thermoregulation during cold exposure appears to be concurrent with the capability to display torpor (i.e. poikilothermy is followed by heterothermy), supporting the view that torpor is phylogenetically old and likely plesiomorphic. In contrast, in small, altricial placental mammals (2 orders), poikilothermy at birth is followed first by a homeothermic phase after endothermic thermoregulation is established; the ability to employ torpor develops later (i.e. poikilothermy-homeothermy-heterothermy). This suggests that in placentals torpor is a derived trait that evolved secondarily after a homeothermic phase in certain taxa perhaps as a response to energetic challenges. As mammals and birds arose from different reptilian lineages, endothermy likely evolved separately in the two classes, and given that the developmental sequence of torpor differs between marsupials and placentals, torpor seems to have evolved at least thrice.     

Environmental health and genomics: visions and implications

The relationship between genes and the environment can be compared to a loaded gun and its trigger. A loaded gun by itself causes no harm; it is only when the trigger is pulled that the potential for harm is released. Genetic susceptibility creates an analogous situation, where the loaded gun is one or a combination of susceptibility genes (alleles) and the trigger is an environmental exposure. The key objective of the Environmental Genome Project is to identify alleles that confer susceptibility to the adverse effects of environmental agents. Here we discuss the goals of the Environmental Genome Project, its implications and, in particular, its potential effect on our ability to assess human disease risk in the future.     

Mechanisms and function of flower and inflorescence reversion

Flower and inflorescence reversion involve a switch from floral development back to vegetative development, thus rendering flowering a phase in an ongoing growth pattern rather than a terminal act of the meristem. Although it can be considered an unusual event, reversion raises questions about the nature and function of flowering. It is linked to environmental conditions and is most often a response to conditions opposite to those that induce flowering. Research on molecular genetic mechanisms underlying plant development over the last 15 years has pinpointed some of the key genes involved in the transition to flowering and flower development. Such investigations have also uncovered mutations which reduce floral maintenance or alter the balance between vegetative and floral features of the plant. How this information contributes to an understanding of floral reversion is assessed here. One issue that arises is whether floral commitment (defined as the ability to continue flowering when inductive conditions no longer exist) is a developmental switch affecting the whole plant or is a mechanism which assigns autonomy to individual meristems. A related question is whether floral or vegetative development is the underlying default pathway of the plant. This review begins by considering how studies of flowering in Arabidopsis thaliana have aided understanding of mechanisms of floral maintenance. Arabidopsis has not been found to revert to leaf production in any of the conditions or genetic backgrounds analysed to date. A clear-cut reversion to leaf production has, however, been described in Impatiens balsamina. It is proposed that a single gene controls whether Impatiens reverts or can maintain flowering when inductive conditions are removed, and it is inferred that this gene functions to control the synthesis or transport of a leaf-generated signal. But it is also argued that the susceptibility of Impatiens to reversion is a consequence of the meristem-based mechanisms controlling development of the flower in this species. Thus, in Impatiens, a leaf-derived signal is critical for completion of flowering and can be considered to be the basis of a plant-wide floral commitment that is achieved without accompanying meristem autonomy. The evidence, derived from in vitro and other studies, that similar mechanisms operate in other species is assessed. It is concluded that most species (including Arabidopsis) are less prone to reversion because signals from the leaf are less ephemeral, and the pathways driving flower development have a high level of redundancy that generates meristem autonomy even when leaf-derived signals are weak. This gives stability to the flowering process, even where its initiation is dependent on environmental cues. On this interpretation, Impatiens reversion appears as an anomaly resulting from an unusual combination of leaf signalling and meristem regulation. Nevertheless, it is shown that the ability to revert can serve a function in the life history strategy (perenniality) or reproductive habit (pseudovivipary) of many plants. In these instances reversion has been assimilated into regular plant development and plays a crucial role there.     

生物多样性与生态系统服务——关系、权衡与管理

生物多样性和生态系统服务是人类生存和社会经济可持续发展的物质基础,应对生物多样性丧失和生态系统服务退化问题已经成为继气候变化之后的又一个全球性环境热点问题。生物多样性是生态系统生产力、稳定性、抵抗生物入侵以及养分动态的主要决定因素,生物多样性越高,生态系统功能性状的范围越广,生态系统服务质量就越高越稳定。目的是探讨生物多样性和生态系统服务之间的关系:(1)明确了生物多样性与生态系统过程、功能、服务之间的关系;(2)生物多样性在生态系统服务中的角色:生物多样性在不同的空间尺度通过各种形式的运行机制与生态系统服务产生联系,生物多样性是生态系统过程的调节者,是巩固生态系统服务的一个重要因素,生物多样性也是一种终极的生态系统服务,并在遗传和物种水平上直接贡献了其利益和价值;(3)生物多样性与生态系统服务权衡和协同关系的研究可以更好的帮助管理人员做出有利的决策和保护工作,也是制定规划和适应策略以减少生物多样性危机带来的不利影响的基础;(4)生物多样性与生态系统服务的关系在不同的时间和空间尺度上是不恒定的,有必要共同确定生态系统服务和生物多样性的空间格局,以有效和可持续的进行生态系统管理;(5)虽然生物多样性保护和生态系统管理还存在许多不确定性,但相关理论应该在管理、保护和恢复生态系统中发挥重要作用。研究提出了进一步研究的领域,以促进生物多样性保护和生态系统服务提供之间的协同作用。希望对相关领域的研究有所帮助。     

Modeling alignment and movement of animals and cells

 Schools of fish and flocks of birds are examples for groups of individuals moving in a highly organized way. Individuals adapt their orientation and speed to that of their (nearest) neighbors. Adaptation of orientation can also be found on the cellular and subcellular level and is called alignment. A model for alignment and movement is derived on the basis of reaction transport equations in one space dimension. Existence of solutions is shown and long time behavior of the system is described. The effect of schooling on the risk of predation is investigated. Then the model is generalized to two space dimensions and compared to other models for alignment which do not incorporate individual movement in space. Received: 27 March 2001 / Revised version: 17 January 2002 / Published online: 23 August 2002     

Simultaneous extraction of beta-endorphin and leu- and met-enkephalins from human and rat plasma

A simple, rapid and reliable procedure is described to simultaneously concentrate and purify beta-endorphin, leu- and met-enkephalins from small volumes of human and rat plasma before radioimmunoassay is performed. It uses C18 Sep-Pak reverse phase cartridges. The effectiveness of different protease inhibitors in preventing degradation of opiates by plasma and different solvent systems for eluting opiates is also evaluated.     

Content and structure of ceramide and sphingomyelin and sphingomyelinase activity in mouse hepatoma-22

The relative content of phosphatidylcholine is lower and that of sphingomyelin is higher in transplantable fast growing mouse hepatoma-22, thus decreasing their ratio approximately 2.5-fold versus normal liver. The ceramide content and the neutral sphingomyelinase activity is markedly higher (3- and 6.5-fold, respectively), whereas the acid sphingomyelinase activity is 4-fold lower in hepatoma-22 versus normal liver. The content of saturated fatty acids in ceramide and sphingomyelin of hepatoma-22 is higher than in normal liver. All sphingolipids of hepatoma-22 contain a considerable amount (25-37%) of sphinganine (dihydrosphingosine) along with sphingenine (sphingosine), whereas sphingolipids of normal liver contain predominantly sphingenine (over 95%). These results indicate that the activity of enzymes involved in sphingolipid biosynthesis and catabolism is disturbed in the transplantable mouse hepatoma-22 compared to normal liver.