Function of the alternative oxidase: is it still a scavenger?

The alternative oxidase is a respiratory chain protein found in all higher plants, fungi, non-fermentative yeasts and trypanosomes. Its primary structure suggests that it is a new member of the di-iron carboxylate protein family. Recent sequence analysis indicates an evolutionary relationship between primitive members of this protein family and the alternative oxidase, suggesting that its early function was to scavenge di-oxygen. However, modelling of plant growth kinetics suggests a different function.     

Dyspepsia: is a trial of therapy appropriate?

Dyspepsia is a common, benign condition that may be distinguished from gastroesophageal reflux, irritable bowel syndrome and pancreatobiliary, coronary or musculoskeletal disease by a careful history and physical examination. However, the presence or absence of a peptic ulcer in dyspepsia can be determined only by an endoscopic examination or a barium-contrast radiograph. Although the American College of Physicians has recommended trying drug therapy for patients with dyspepsia before diagnostic tests are done, new data support early diagnosis. Although therapy is initially cheaper than endoscopic examination, over a year the costs even out because most patients with dyspepsia eventually need an endoscopic examination, and many patients with nonulcer dyspepsia are given medication unnecessarily. Endoscopic examination, if available to general practitioners, is the most cost-effective approach to dyspepsia. An approach that does not include endoscopy lacks the opportunity to offer patients convincing reassurance that their illness is not serious, which is arguably the most important treatment in cases of nonulcer dyspepsia. Studies supporting the use of endoscopic examination predate the treatment of peptic ulcers with antibiotics, which makes an initial endoscopic examination to determine whether the patient has an ulcer even more important.     

The antihypertensive effect of peptides: a novel alternative to drugs?

Many types of bioactive peptides that inhibit angiotensin I, angiotensin I converting enzyme (ACE) and Ang II type 1 receptor (AT1) in the cardiovascular system contribute to the prevention and treatment of hypertension. These inhibitory peptides are derived from many food proteins or artificial synthetic products. Further research examining the bioavailability of ACE inhibitory peptides will lead to the development of more effective ACE inhibitory peptides and foods. Our research also demonstrates that ACE inhibitory peptide LAP may lower blood pressure with no adverse effects.     

Evolution of alternative male morphotypes in oxyurid nematodes: a case of convergence?

Male dimorphism has been reported across different taxa and is usually expressed as the coexistence of a larger morph with exaggerated male traits and a smaller one with reduced traits. The evolution and maintenance of male dimorphism are still poorly understood for several of the species in which it has been observed. Here, we analyse male dimorphism in several species of reptile parasitic nematodes of the genus Spauligodon, in which a major male morph (exaggerated morph), which presents the traditional male morphological traits reported for this taxon, coexists with a minor morph with reduced morphological traits (i.e. reduced genital papillae) resembling more closely the males of the sister genus Skrjabinodon than Spauligodon major males. Because of the level of uncertainty in the results of ancestral state reconstruction, it is unclear if the existence of male dimorphism in this group represents independent instances of convergent evolution or an ancestral trait lost multiple times. Also, although the number of major males per host was positively correlated with the number of females, the same did not hold true for minor males, whose presence was not associated with any other ecological factor. Nevertheless, the existence of male dimorphism in Spauligodon nematodes is tentatively interpreted as resulting from alternative reproductive tactics, with differences in presence and number of individuals as indicators of differences in fitness, with the lower numbers of minor males per host likely maintained by negative frequency‐dependent selection.     

Oxidation of proteins: is it a programmed process?

Proteins represent extremely susceptible targets for oxidants. Oxidative modifications of proteins may bring about violation of their structure and functionality. It implies that the structures of proteins are not infallible in terms of their antioxidant defence. The protection mechanisms in preventing oxidative damages for proteins within cells are mainly related to a large variety of antioxidant enzymatic systems. In contrast, plasma proteins are scarcely protected by these systems, so the mechanism that provides their functioning in the conditions of generating reactive oxygen species (ROS) seems to be much more complicated. Oxidation of many proteins was long considered as a random process. However, the highly site-specific oxidation processes was convincingly demonstrated for some proteins, indicating that protein structure could be adapted to oxidation. According to our hypothesis, some of the structural elements present in proteins are capable of scavenging ROS to protect other protein structures against ROS toxicity. Various antioxidant elements (distinct subdomains, domains, regions, and polypeptide chains) may act as ROS interceptors, thus mitigating the ROS action on functionally crucial amino acid residues of proteins. In the review, the oxidative modifications of certain plasma proteins, such as α₂-macroglobulin, serum human albumin, fibrinogen, and fibrin-stabilising factor, which differ drastically in their spatial structures and functions, are analysed. The arguments that demonstrate the possibility of existing hypothetical antioxidant structures are presented. For the first time, the emphasis is being placed on the programmed mechanism of protein oxidation.     

Synaptic vesicles: is kissing a matter of competence?

The "kiss-and-run" model of exocytosis and endocytosis predicts that synaptic vesicles can undergo fast and efficient recycling, after fusion with the plasmalemma, without intermixing of membranes. Evidence is mounting from several new experimental approaches that kiss-and-run occurs at synapses. Distinct vesicle pools, which initially were identified in morphological terms, are now being characterized in biochemical and functional terms. In addition, at least two functional recycling pathways, operating on different time scales (from milliseconds to tens of seconds), have been shown to coexist in the same synaptic system, and the two pathways appear to be differentially regulated. Taken together, these data suggest that kiss-and-run operates in parallel with the classical, coated-vesicle recycling. Here, we review recent evidence for kiss-and-run recycling and discuss whether it is a distinct process, dependent on the molecular organization of the fusing vesicle. We propose that vesicles undergo a process of "competence maturation". According to this view, the specific molecular make-up of the vesicles, their location and their interactions with nerve terminal proteins might determine not only the differential availability of the vesicles for fusion and neurotransmitter release but also the recycling path that they will follow.     

Alfalfa infection model: is it a potential alternative for mouse pneumonia model to study pathogenesis of Stenotrophomonas maltophilia?

The objective of this study was to develop a new, inexpensive and simple plant model to study the virulence potential of Stenotrophomonas maltophilia. The alfalfa seedlings were visually monitored for disease symptoms till 7 days post infection with 10⁵ cfu/ml of five different strains (Sm1–Sm5) of S. maltophilia. Symptoms including yellowing of leaves, stunted roots, and brown necrotic regions on seedlings were considered as disease symptoms. Sm5 and Sm2 appeared to be most virulent in alfalfa infection model, whereas Sm3 and Sm4 were moderately virulent. Strain Sm1 was found to be weakly virulent. A comparison of alfalfa infection model was carried out with mouse pneumonia model to compare the virulence of different strains of S. maltophilia in both models. Although there was variability in the level of infection caused by different strains, in both models of study, strains Sm5 and Sm2 appeared to be most virulent and were able to cause a comparatively more severe infection. We conclude that both the models can be used to study the pathogenesis of S. maltophilia and to analyze the preliminary virulence potential of this bacterium. However, clearly, to study the virulence factors, a mouse pneumonia model would be desirable.     

Cyclopentane-nucleobase coupling in the synthesis of carbocyclic L-nucleosides: is a SN2-reaction an alternative to the Mitsunobu-reaction?

Several carbocyclic L-nucleosides have been synthesized by coupling a cyclopentane-system with heterocycles according to a modified Mitsunobu-protocol. This reaction gave two regioisomers, the N1-alkylated product and an unwanted O(2)-product. A simple S(N)2-reaction has been investigated as an alternative for such couplings.     

Logic of experiments in ecology: is pseudoreplication a pseudoissue?

Hurlbert divides experimental ecologist into ‘those who do not see any need for dispersion (of replicated treatments and controls), and those who do recognize its importance and take whatever measures are necessary to achieve a good dose of it’. Experimental ecologists could also be divided into those who do not see any problems with sacrificing spatial and temporal scales in order to obtain replication, and those who understand that appropriate scale must always have priority over replication. If an experiment is conducted in a spatial or temporal scale, where the predictions of contesting hypotheses are convergent or ambiguous, no amount of technical impeccability can make the work instructive. Conversely, replication can always be obtained afterwards, by conducting more experiments with basically similar design in different areas and by using meta‐analysis. This approach even reduces the sampling bias obtained if resources are allocated to a small number of well‐replicated experiments. For a strict advocate of the hypothetico‐deductive method, replication is unnecessary even as a matter of principle, unless the predicted response is so weak that random background noise is a plausible excuse for a discrepancy between predictions and results. By definition, a prediction is an ‘all‐statement’, referring to all systems within a well‐defined category. What applies to all must apply to any. Hence, choosing two systems and assigning them randomly to a treatment and a control is normally an adequate design for a deductive experiment. The strength of such experiments depends on the firmness of the predictions and their a priori probability of corroboration. Replication is but one of many ways of reducing this probability. Whether the experiment is replicated or not, inferential statistics should always be used, to enable the reader to judge how well the apparent patterns in samples reflect real patterns in statistical populations. The concept ‘pseudoreplication’ amounts to entirely unwarranted stigmatization of a reasonable way to test predictions referring to large‐scale systems.     

What is a 'low dose' of radiation?

Although the expression of radiation-induced biological effects and responses may be at either the cell, organ or organism level, induction of some of these phenomena (e.g. cancer of clastogenic and genetic effects) can have their origin in the interaction of a single charged particle with the target-containing volume (TCV) of the cell, e.g. the cell nucleus. However, the independent variable now used in both organ and cell population studies, the absorbed dose to the organ, provides no information directly on particle-TCV interactions. Even if calculated as a mean to an organized population of cells, the absorbed dose becomes a composite and confounded quantity, (FzN), in which F is the fraction of TCVs 'hit' by a particle during a given exposure, z is the mean value of z1, the energy absorbed in the TCV in a single hit, and N is the mean number of hits per affected TCV. Scientific precepts demand the avoidance of such confounded variables by achieving their isolation. The needed separation can be effected by the use of microdosimetric techniques, which make it possible to hold one component quantity constant while the others are varied. As an example, low-level radiation exposure (LLE) can be used to hold F at a constant value of 0.2 where, on average, there is but one hit per TCV. The probability of a cellular quantal response, as a function of z1 only, can then be determined by use of LLE to radiations covering a wide span of LETs. Conversely, the effect of varying only the fraction of cells hit can be studied by holding z constant. This can be accomplished by working within a narrow band of LET, but only in the LLE range. The effectiveness of preirradiation altering cell sensitivity as a function of the number of hits per TCV can be determined by working within, and somewhat above, the LLE range. In either risk assessment or the application of radiation as a pretreatment, minimal consequences can be assured only if very low-level exposure is employed in order that F will be small, and if the exposure is in a field of radiation of very low LET so that z1 will be as small as possible. That is to say, exposure conditions with low consequences cannot be specified in terms of any single quantity.     

Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction?

The aim of this study was to understand the mechanism of action through which carnosine (beta-alanyl-L-histidine) acts as a quencher of cytotoxic alpha,beta-unsaturated aldehydes, using 4-hydroxy-trans-2,3-nonenal (HNE) as a model aldehyde. In phosphate buffer solution (pH 7.4), carnosine was 10 times more active as an HNE quencher than L-histidine and N-acetyl-carnosine while beta-alanine was totally inactive; this indicates that the two constitutive amino acids act synergistically when incorporated as a dipeptide and that the beta-alanyl residue catalyzes the addition reaction of the histidine moiety to HNE. Two reaction products of carnosine were identified, in a pH-dependent equilibrium: (a) the Michael adduct, stabilized as a 5-member cyclic hemi-acetal and (b) an imine macrocyclic derivative. The adduction chemistry of carnosine to HNE thus appears to start with the formation of a reversible alpha,beta-unsaturated imine, followed by ring closure through an intra-molecular Michael addition. The biological role of carnosine as a quencher of alpha,beta-unsaturated aldehydes was verified by detecting carnosine-HNE reaction adducts in oxidized rat skeletal muscle homogenate.     

Global biogeography of autotroph chemistry: is insolation a driving force?

Synthesis The tissue chemistry of plants can influence ecosystem processes including growth, herbivory, and decomposition. Our comparison of nitrogen and phosphorus in over 1700 autotroph taxa demonstrates that latitudinal trends in tissue chemistry are consistent across non‐vascular and vascular species in freshwater, terrestrial, and marine ecosystems. Tissue chemistry varies most within species and taxonomic lineages, yet the nitrogen to phosphorus ratio within individuals is strikingly similar among species in different ecosystems. These results shed new light on existing hypotheses, suggesting that light (e.g. photon flux) and growing season duration are primary drivers of latitudinal gradients in tissue chemistry, but providing little support for temperature, nutrient supply, or soil substrate age. Photoautotroph nitrogen (N) and phosphorus (P) tissue concentrations can influence ecosystem function via processes including growth, decomposition, and consumption, and may reflect traits maintaining coexistence. Studies in terrestrial systems have led to hypotheses that latitudinal trends in the N and P content of leaves may be driven by soil substrate age, environmental temperature, or season length; however, terrestrial patterns alone cannot differentiate these mechanisms. Here, we demonstrate that broad geographical patterns of N and P in freshwater and marine multicellular photoautotrophs are concordant with those in terrestrial ecosystems. Our > 6800 record database reveals that mean tissue N and P increase with latitude in all ecosystems, but P increases more rapidly, causing N:P to decline; mean N:P scaling within individuals also is identical among systems, despite very different evolutionary environments. A partitioning of the variance in these data suggests that species composition and local environmental context likely lead to the variation observed within a latitudinal band. However, the consistency of trends in photosynthetic tissue chemistry across Earth’s ecosystems suggests that biogeographical gradients in insolation and growing season length may constrain tissue N and P, whereas global trends in temperature, nutrient supply, and soil substrate age are unlikely to generate the consistent latitudinal trends among ecosystems. Thus, this cross‐ecosystem comparison suggests a new hypothesis, global patterns of insolation, while also providing a new perspective on other mechanisms that have been hypothesized to underlie latitudinal trends in photosynthetic tissue chemistry.     

Integrin adhesion: when is a kinase a kinase?

Recent genetic studies in the worm Caenorhabditis elegans and fruitfly Drosophila have revealed the essential role integrin-linked kinase plays in integrin adhesion - but it apparently acts in this role as an adaptor rather than a kinase.