The purine nucleoside cycle in cell-free extracts of rat brain: evidence for the occurrence of an inosine and a guanosine cycle with distinct metabolic roles

The purine nucleoside cycle is a cyclic pathway composed of three cytosolic enzymes, hypoxanthine-guanine phosphoribosyltransferase, IMP-GMP specific 5'-nucleotidase, and purine-nucleoside phosphorylase. It may be considered a 'futile cycle', whose net reaction is the hydrolysis of 5-phosphoribosyl-1-pyrophosphate to inorganic pyrophosphate and ribose 1-phosphate. The availability of a highly purified preparation of cytosolic 5'-nucleotidase prompted us to reconstitute the purine nucleoside cycle. Its kinetics were strikingly similar to those observed when dialyzed extracts of rat brain were used. Thus, when the cycle is started by addition of inorganic phospate (Pi) and hypoxanthine or inosine (the 'inosine cycle'), steady-state levels of the intermediates are observed and the cycle 'turns over' as far as 5-phosphoribosyl-1-pyrophosphate is being consumed. In the presence of ATP, which acts both as an activator of IMP-GMP-specific 5'-nucleotidase and as substrate of nucleoside mono- and di-phosphokinases, no IDP and ITP are formed. The inosine cycle is further favored by the extremely low xanthine oxidase activity. Evidence is presented that ribose 1-phosphate needed to salvage pyrimidine bases in rat brain may arise, at least in part, from the 5-phosphoribosyl-1-pyrophosphate hydrolysis as catalyzed by the inosine cycle, showing that it may function as a link between purine and pyrimidine salvage. When the cycle is started by addition of Pi and guanine (the 'guanosine cycle'), xanthine and xanthosine are formed, in addition to GMP and guanosine, showing that the guanosine cycle 'turns over' in conjunction with the recycling of ribose 1-phosphate for nucleoside interconversion. In the presence of ATP, GDP and GTP are also formed, and the velocity of the cycle is drastically reduced, suggesting that it might metabolically modulate the salvage synthesis of guanyl nucleotides.     

Calcitonin-like peptide in the shrimpPalaemon serratus (Crustacea,Decapoda) during the intermolt cycle

Summary A molecule immunologically related to salmon calcitonin has been detected in the hemolymph of the shrimpPalaemon serratus. Its concentration varies inversely with the calcium level during the molt cycle; a maximum (14 ng/ml) is found in the post-molt stage and a minimum (0.5 ng/ml) during the premolt stage.     

<Emphasis Type="Italic">Legionella pneumophila</Emphasis> — a human pathogen that co-evolved with fresh water protozoa

The bacterial pathogen Legionella pneumophila is found ubiquitously in fresh water environments where it replicates within protozoan hosts. When inhaled by humans it can replicate within alveolar macrophages and cause a severe pneumonia, Legionnaires disease. Yet much needs to be learned regarding the mechanisms that allow Legionella to modulate host functions to its advantage and the regulatory network governing its intracellular life cycle. The establishment and publication of the complete genome sequences of three clinical L. pneumophila isolates paved the way for major breakthroughs in understanding the biology of L. pneumophila. Based on sequence analysis many new putative virulence factors have been identified foremost among them eukaryotic-like proteins that may be implicated in many different steps of the Legionella life cycle. This review summarizes what is currently known about regulation of the Legionella life cycle and gives insight in the Legionella-specific features as deduced from genome analysis. Received 1 September 2006; received after revision 10 October 2006; accepted 22 November 2006     

Flagellin glycosylation with pseudaminic acid in <Emphasis Type="Italic">Campylobacter</Emphasis> and <Emphasis Type="Italic">Helicobacter</Emphasis>: prospects for development of novel therapeutics

Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme–substrate and –inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.     

Cattle grazing behavior regulates tick populations

Summary Analysis of field population data showed that host-seeking larvae of the tickBoophilus microplus were less successful in attaching to their hosts when larval densities were high. Experimental results showed that cattle hosts detected and avoided high densities of larvae in pasture. The finding reveals a previously unknown population-regulating mechanism for ticks, which are important pests of livestock.Acknowledgment. The authors wish to thank G. Maywald, D. Stegeman, R. Tozer, A. Voll, G. Milne and J. Osborne who helped with the observations. The Australian Meat Research Committee (AMRC) and the Australian Centre for International Agricultural Research (ACIAR) provided some financial support for the project and A. Edwards assisted greatly with the photography.     

The adaptive significance of sexuality

A theory of sexuality and polymorphism is proposed in which diversity at the molecular level is the adaptive response of multicellular organisms to the challenge of microparasites that have smaller genomes, shorter generation times and which can evolve more quickly than their hosts. The theory has implications for genetically homogenized crops and other cultivated plants as well as for immunology. A different function of sexuality is proposed for microorganisms that reproduce both asexually and sexually. Several possible experimental tests are discussed. Mathematical modelling techniques are outlined qualitatively and compared with game-theoretical methods which may be interpreted as simplifications of population dynamics of polymorphic host-parasite populations are referenced.     

A simple method of preparing chick eggs for chorio-allantoic grafts

Summary A method of preparing chick hosts for receiving grafts to the chorio-allantoic membrane (CAM) is described, which is quicker and requires less manipulative skill than that in general use.     

The adaptive significance of sexuality

Summary A theory of sexuality and polymorphism is proposed in which diversity at the molecular level is the adaptive response of multicellular organisms to the challenge of microparasites that have smaller genomes, shorter generation times and which can evolve more quickly than their hosts. The theory has implications for genetically homogenized crops and other cultivated plants as well as for immunology. A different function of sexuality is proposed for microorganisms that reproduce both asexually and sexually. Several possible experimental tests are discussed. Mathematical modelling techniques are outlined qualitatively and compared with game-theoretical methods which may be interpreted as simplifications of population dynamic and genetic equilibria. Some results about equilibria, stability and extinction in the population dynamics of polymorphic host-parasite populations are referenced.     

Die Alkoholdehydrogenase Ihre Wirkungsweisen und Komplexverbindungen

Summary Liver alcohol dehydrogenase (LADH) is one of the most intensely studied of all enzymes because it is easily available in crystalline form and has many properties which are favourable for experimentation. Its mode of action has been elucidated to some extent mainly by kinetic experiments with and without inhibitors.Its substrate specificity is very low, since the enzyme attacks a great variety of primary and secondary alcohols, or reversibly aldehydes and ketones. Its main physiological function is still unknown, but may be found by the aid of pyrazole which acts as a specific inhibitor in vivo.Complexes of the enzyme with coenzyme, or coenzyme + inhibitors have been crystallized and are presently being studied by X-ray crystallography in the hope of determining the three-dimensional structure of the molecule. The formation of the ternary complexes leads to a profound change of conformation (monoclinic instead ofortho-rhombic crystals). Simultaneously the optical rotatory dispersion is drastically changed.

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Paul-Karrer-Vorlesung, gehalten am 30. Juni 1965, an der Universität Zürich (Schweiz).     

Hsp70 chaperones: Cellular functions and molecular mechanism

Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.Received 21 October 2004; received after revision 24 November 2004; accepted 6 December 2004     

The orthodox-paradoxical sleep cycle in the rat.

Under the postulated existence of a mechanism regulating the NREM sleep- REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset.     

Numerical variation of ciliated papillae in the miracidia of different strains of Schistosoma mansoni, the organism producing intestinal bilharzia]

In the miracìdia of 13 strains of Schistosoma mansoni, silver impregnation points out variations in the number of ciliated papillae situated between tiers 2 and 3 of epidermal cells, correlative with the size of the miracidia. These variations are related to the intermediate and definitive hosts. The number of ciliated papillae gives objective information on the degree of adaptation between the parasite and its successive hosts.     

Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees

Two African species of Aspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.     

月球轨道器交会对接同波束VLBI测量差分相时延实时解算

同波束VLBI技术是解决月球轨道交会对接地面高精度引导的重要手段．传统的多频点同波束VLBI实时解算算法成功解算差分相位整周模糊度的概率较低,而事后统计修正求解整周模糊度的算法存在较大的时间滞后,从而直接影响月球轨道交会对接两个航天器地面定轨、定位的精度以及实时性．在此背景下,本文研究了应用于月球交会对接条件下的同波束VLBI差分相时延实时解算算法．首先给出了多频点同波束VLBI解算差分相时延及整周模糊度的原理,根据差分相关相位整周模糊和差分相时延实时及事后解算结果,对整周模糊度产生的原因进行分析通过求解精确差分群时延值、采用匹配搜索算法以及差分相位连接条件对传统实时解算算法进行改进,提出一种新的差分相时延实时解算算法．利用SELENE同波束VLBI观测数据进行实时解算．结果表明该算法成功解算模糊度的准确度达到95．49％,相对于传统解算算法准确度提高了5．45％．     

The orthodox-paradoxical sleep cycle in the rat

Summary Under the postulated existence of a mechanism regulating the NREM sleep-REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset.     

Thiarubrine A,a bioactive constituent ofAspilia (Asteraceae) consumed by wild chimpanzees

Summary Two African species ofAspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.     

Introducing the Euro Area‐wide Leading Indicator (ALI): Real‐Time Signals of Turning Points in the Growth Cycle from 2007 to 2011

This paper introduces a new monthly euro Area‐wide Leading Indicator (ALI) for the euro area growth cycle which is composed of nine leading series and derived from a one‐sided bandpass filter. The main findings are that (i) the GDP growth cycle in the euro area can be well tracked, in a timely manner and at monthly frequency, by a reference growth cycle indicator (GCI) derived from industrial production excluding construction, (ii) the ALI reliably leads turning points in the GCI by 5 months and (iii) longer leading components of the ALI are good predictors of the GCI up to 9 months ahead. A real‐time case study on the ALI's capabilities for signalling turning points in the euro area growth cycle from 2007 to 2011 confirms these findings. Copyright © 2013 John Wiley & Sons, Ltd.     

Geminivirus DNA replication

Geminiviruses are DNA viruses which infect plants. They have a small genome and encode only a few proteins. Therefore, their DNA replication cycle relies largely on the use of cellular DNA replication proteins. The strategy used by geminiviruses to replicate their single-stranded DNA (ssDNA) genome consists of a first stage of conversion of ssDNA into double-stranded DNA (dsDNA) intermediates and, then, the use of dsDNA as a template to amplify viral dsDNA and to produce mature ssDNA genomes by a rolling-circle replication mechanism. In addition, the accumulating evidence indicates that viral DNA replication is somehow coupled to the cell cycle regulatory network of the infected cell. For these reasons, geminiviruses are excellent model systems to understand the regulation of DNA replication and cell cycle in plant cells. Recent years have witnessed significant progress in the identification of cis-acting signals and their interaction with trans-acting factors that contribute to geminivirus origin function. These and other aspects of the geminivirus DNA replication cycle will be reviewed.