Genetic code 1990. Outlook

The genetic code is evolving as shown by 9 departures from the universal code: 6 of them are in mitochondria and 3 are in nuclear codes. We propose that these changes are preceded by disappearance of a codon from coding sequences in mRNA of an organism or organelle. The function of the codon that disappears is taken by other, synonymous codons, so that there is no change in amino acid sequences of proteins. The deleted codon then reappears with a new function. Wobble pairing between anticodons and codons has evolved, starting with a single UNN anticodon pairing with 4 codons. Directional mutation pressure affects codon usage and may produce codon reassignments, especially of stop codons. Selenocysteine is coded by UGA, which is also a stop codon, and this anomaly is discussed. The outlook for discovery of more changes in the code is favorable, and open reading frames should be compared with actual sequential analyses of protein molecules in this search.     

Beyond blood pressure: new roles for angiotensin II

Since the discovery 100 years ago by Tigerstedt and Bergman of renin, an acid protease generating angiotensin peptide, numerous discoveries have advanced our understanding of the renin-angiotensin system (RAS). The recent cloning of angiotensin receptors and the availability of specific receptor ligands have allowed characterization of angiotensin-receptor-mediated actions, and an increasing number of studies using biochemical, pharmacological and molecular biological methods has focused on the many different physiological actions of the RAS in various tissues. Angiotensin II, the main effector peptide of the RAS, exerts most of its known actions in blood pressure control and body fluid homeostasis via the AT, receptor. AT, receptors not only play a role in growth control and cell differentiation but have been implicated in apoptosis and tissue regeneration. This review focuses on the extrarenal functions of angiotensin, especially in neuronal cells and the nervous system, and on recent advances in angiotensin receptor research.     

Suppression and the code: beyond codons and anticodons

Specificity and accuracy in the decoding of genetic information during mRNA-programmed, ribosome-dependent polypeptide synthesis (translation) involves more than just hydrogen bonding between two anti-parallel trinucleotides, the mRNA codon and the tRNA anticodon. Other macromolecules are also involved, and translational suppression has been and continues to be an appropriate and effective way to identify them, as well as other parts of mRNA and tRNA, and to elucidate the structural determinants of their functions and interactions. Experimental results are presented that bear upon codon context effects, the role of tRNA structural features in aminoacyl-tRNA selection and in codon selection (reading-frame maintenance), determinants of tRNA identity, elongation factor suppressor mutants, and termination codon recognition by the ribosomal RNA of the small subunit. The examples presented illustrate the complexity of the decoding process and the interconnectedness of translational macromolecules in achieving specificity and accuracy in polypeptide synthesis.     

The genetic code in mitochondria and chloroplasts

The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.     

Regional vascular reactivity in rats with Guérin carcinoma (GC)

Summary Increased sensitivity to phenylephrin and a decreased one to isoproterenol has been found in regional vascular beds of GC implanted rats. Circulatory sympathetic reflex adaptation, alfa- and beta-adrenergic stimulation or blockade provoked a uniform response pattern: i.e. increase in vascular resistance of GC.     

Regional vascular reactivity in rats with Guérin carcinoma (GC).

Increased sensitivity to phenylephrin and a decreased one to isoproterenol has been found in regional vascular beds of GC implanted rats. Circulatory sympathetic reflex adaptation, alfa- and beta-adrenergic stimulation or blockade provoked a uniform response pattern: i.e. increase in vascular resistance of GC.     

Mating attempts between the Scarlet Tiger Moth,Callimorpha dominula L., and the Cinnabar Moth,Tyria jacobaeae L. (Lepidoptera: Arctiidae), involve a common sex pheromone composition

It has been suggested that a common sex pheromone composition may account for interspecific sexual interactions observed with certain moths in the Arctiidae. In this study, it is demonstrated that the sex pheromones released by females of the Scarlet Tiger Moth,Callimorpha dominula L., and the Cinnabar Moth,Tyria jacobaeae L., have similar activities and elute at the same retention time on analysis by coupled gas chromatography (GC)-electrophysiology with males from each species. Peak enhancement on GC, chiral GC and coupled GC-mass spectrometry using authentic compounds show that the sex pheromone for bothC. dominula andT. jacobaeae is (3Z,6Z,9S,10R)-9,10-epoxyheneicosa-3,6-diene.     

What’s new in the renin-angiotensin system?

The angiotensin AT(4) receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT(4) receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na(+) transport in isolated renal proximal tubules. The AT(4) receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT(4) receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.     

基于FLUENT的高压气体检测雷管空管体的流场分析

基于计算流体力学,借助软件Fluent建立了高压气体检测空管体暗伤的简化模型,并对暗伤处的流场进行了数值模拟分析,针对被氧化膜覆盖的暗伤进行检测,对提高检测的速度和准确性具有十分的积极意义。     

Aminoglycoside antibiotics: old drugs and new therapeutic approaches

Aminoglycoside antibiotics kill bacteria by binding to the ribosomal decoding site and reducing fidelity of protein synthesis. Since the discovery of these natural products over 50 years ago, aminoglycosides have provided a mainstay of antibacterial therapy of serious Gram-negative infections. In recent years, aminoglycosides have become important tools to study molecular recognition of ribonucleic acid (RNA). In an ingenious exploitation of the aminoglycosides’ mechanism of action, it has been speculated that drug-induced readthrough of premature stop codons in mutated messenger RNAs might be used to treat patients suffering from certain heritable genetic disorders. Received 23 January 2007; received after revision 25 February 2007; accepted 29 March 2007     

What’s new in the renin-angiotensin system?

The type 1 angiotensin receptor (AT(1)) activates an array of intracellular signalling pathways that control cell and tissue responses to the peptide hormone angiotensin II (AngII). The capacity of AT(1) receptors to initiate and maintain such signals has typically been explained on the basis of conventional heterotrimeric guanine nucleotide binding protein (G protein) activation, specifically G(q/11). Accumulating evidence from studies utilising a variety of AT(1) receptor mutants and AngII analogues indicates that some important downstream effects of AT(1) receptors are independent of classical G protein coupling. Importantly, AT(1) receptor-mediated endocytosis, tyrosine phosphorylation signalling and mitogen-activated protein kinase activation as well as transactivation of the epidermal growth factor receptor can occur in G(q/11)-uncoupled receptor mutants. These observations point to a functional partitioning of AT(1) receptor signals that permits separation of short-term AngII actions (e.g., vasoconstriction) from more extended events, such as pathological cell growth in heart and blood vessels, and may open up new avenues for selective antagonism.     

The structure of gephyrotoxin (GTX) 223AB

Summary The structure 3-butyl-5-propylindolizidine (2), tentatively assigned to a minor alkaloid in skin extracts from a number of poison frogs of the Neotropical genusDendrobates, has been confirmed and its stereochemistry determined as 5E, 9E (2d) by comparison on GC and GC-MS with the four synthetic diastereomers2a-2d.     

Pyrrolizidine alkaloids in overwintering monarch butterflies (Danaus plexippus) from mexico

Summary North American populations of the monarch butterfly,Danaus plexippus, have been found to contain pyrrolizidine alkaloids and their N-oxides. Analytical methods (TLC, GC, and GC/MS) have been developed to isolate, quantitate, and structurally elucidate the alkaloids. Examples of at least two classes of pyrrolizidine alkaloids have been identified, the macrocyclic diesters, senecionine, integerrimine, and seneciphylline, and the monoesters, echinatine, intermedine, and lycopsamine.21 November 1986This work was supported by NSF (Grants BSR-81-19391 and BSR-81-19382), and a Stauffer Chemical Company fellowship. We thank David Hodapp, Mark Stelljes, and Cordula Bruenner for technical help, Dr T.P. Krick, University of Minnesota, St. Paul, Minn., USA, for assistance in GC/MS analysis of PAs, and Dr J.A. Edgar, CSIRO, Parkville, Victoria, Australia, for samples of authentic reference compounds.     

沾化凹陷异常高压分布特征及其成因机制探讨

采用声波时差法计算沾化凹陷沙三、沙四段的地层压力。发现异常高压纵向上存在两个独立的异常高压系统,规模较大、持续活动强的断层往往是异常高压区的边界,并起到泄压的作用。平面上,以洼陷为中心形成异常高压区,向外逐渐过渡为正常压力带。从沙三上段至沙三四上段,异常高压范围经历了一个扩张-萎缩的旋回,沙三下段凹陷内异常高压分布面积达到最大。对沾化凹陷新生代沉降史及生排烃史的研究表明,较高的沉积速率及有机质生烃是沾化凹陷异常高压发育的主要因素。构造作用通过断层泄压、控制沉积速率及有机质展布起到对异常高压分布直接或间接的控制作用。     

The structure and function of initiation factors in eukaryotic protein synthesis

Protein synthesis is one of the most complex cellular processes, involving numerous translation components that interact in multiple sequential steps. The most complex stage in protein synthesis is the initiation process. It involves initiation factor-mediated assembly of a 40S ribosomal subunit and initiator tRNA into a 48S initiation complex at the initiation codon of an mRNA and subsequent joining of a 60S ribosomal subunit to form a translationally active 80S ribosome. The basal set of factors required for translation initiation has been determined, and biochemical, genetic, and structural studies are now beginning to reveal details of their individual functions in this process. The mechanism of translation initiation has also been found to be influenced significantly by structural properties of the 5' and 3' termini of individual mRNAs. This review describes some of the major developments in elucidating molecular details of the mechanism of initiation that have occurred over the last decade.     

Invariant natural killer T cells in adipose tissue: novel regulators of immune-mediated metabolic disease

Adipose tissue (AT) represents a microenvironment where intersection takes place between immune processes and metabolic pathways. A variety of immune cells have been characterized in AT over the past decades, with the most recent addition of invariant natural killer T (iNKT) cells. As members of the T cell family, iNKT cells represent a subset that exhibits both innate and adaptive characteristics and directs ensuing immune responses. In disease conditions, iNKT cells have established roles that include disorders in the autoimmune spectrum in malignancies and infectious diseases. Recent work supports a role for iNKT cells in the maintenance of AT homeostasis through both immune and metabolic pathways. The deficiency of iNKT cells can result in AT metabolic disruptions and insulin resistance. In this review, we summarize recent work on iNKT cells in immune regulation, with an emphasis on AT-resident iNKT cells, and identify the potential mechanisms by which adipocytes can mediate iNKT cell activity.     

What’s new in the renin-angiotensin system?

Activation of the type 1 angiotensin II receptor (AT(1)R) is associated with the aetiology of left ventricular hypertrophy, although the exact intracellular signalling mechanism(s) remain unclear. Transactivation of the epidermal growth factor receptor (EGFR) has emerged as a central mechanism by which the G protein-coupled AT(1)R, which lacks intrinsic tyrosine kinase activity, can stimulate the mitogen-activated protein kinase signalling pathways thought to mediate cardiac hypertrophy. Current studies support a model whereby AT(1)R-dependent transactivation of EGFRs on cardiomyocytes involves stimulation of membrane-bound metalloproteases, which in turn cleave EGFR ligands such as heparin-binding EGF from a plasma membrane-associated precursor. Numerous aspects of the 'triple membrane-passing signalling' paradigm of AT(1)R-induced EGFR transactivation remain to be characterised, including the identity of the specific metalloproteases involved, the intracellular mechanism for their activation and the exact EGFR subtypes required. Here we examine how 'hijacking' of the EGFR might explain the ability of the AT(1)R to elicit the temporally and qualitatively diverse responses characteristic of the hypertrophic phenotype, and discuss the ramifications of delineating these pathways for the development of new therapeutic strategies to combat cardiac hypertrophy.     

Hydrogen peroxide protects tobacco from oxidative stress by inducing a set of antioxidant enzymes

Tolerance against oxidative stress generated by high light intensities or the catalase inhibitor aminotriazole (AT) was induced in intact tobacco plants by spraying them with hydrogen peroxide (H₂O₂). Stress tolerance was concomitant with an enhanced antioxidant status as reflected by higher activity and/or protein levels of catalase, ascorbate peroxidase, guaiacol peroxidases, and glutathione peroxidase, as well as an increased glutathione pool. The induced stress tolerance was dependent on the dose of H₂O₂ applied. Moderate doses of H₂O₂ enhanced the antioxidant status and induced stress tolerance, while higher concentrations caused oxidative stress and symptoms resembling a hypersensitive response. In stress-tolerant plants, induction of catalase was 1.5-fold, that of ascorbate peroxidase and glutathione peroxidase was 2-fold, and that of guaiacol peroxidases was approximately 3-fold. Stress resistance was monitored by measuring levels of malondialdehyde, an indicator of lipid peroxidation. The levels of malondialdehyde in all H₂O₂-treated plants exposed to subsequent high light or AT stress were similar to those of unstressed plants, whereas lipid peroxidation in H₂O₂-untreated plants stressed with either high light or AT was 1.5- or 2-fold higher, respectively. Although all stress factors caused increases in the levels of reduced glutathione, its levels were much higher in all H₂O₂-pretreated plants. Moreover, significant accumulation of oxidized glutathione was observed only in plants that were not pretreated with H₂O₂. Extending the AT stress period from 1 to 7 days resulted in death of tobacco plants that were not pretreated with H₂O₂, while all H₂O₂-pretreated plants remained little affected by the prolonged treatment. Thus, activation of the plant antioxidant system by H₂O₂ plays an important role in the induced tolerance against oxidative stress. Received 11 December 2001; received after revision 25 January 2002; accepted 4 February 2002     

The effect of nicotine on blood pressure in the genetically hypertensive mouse

Summary Mice genetically selected for high and low blood pressure were exposed to nicotine via a single injected dose or addition to drinking water for 52 weeks. In the acute study, the response of mice with high blood pressure was a statistically significant increase in blood pressure. In the chronic study the pattern of response to nicotine ingestion was similar for mice with high blood pressure and those with low. Both lines responded with an increase in blood pressure after 6 weeks followed by a decrease to below baseline blood pressure at 12 weeks.This research was supported in part by an allocation from the General Research Fund of the University of Kansas.