Biological Signaling Systems Research Articles

Signaling Health versus Parasites

The Hamilton-Zuk hypothesis, that parasite-host coevolution can maintain heritable variation in fitness, has inspired a very successful research program on sexual selection on signals of health. The immunocompetence handicap hypothesis was developed to provide a handicapping mechanism to stabilize the correlation between signals and health. In earlier articles, I showed that handicap signaling is a special case, not a general law that we can rely on to deduce relative costs across signalers of different quality at equilibrium. The essential requirement for reliable signaling is that higher-quality signalers are more efficient; they get greater marginal fitness returns from an incremental increase in the signal. This does not undermine the Hamilton-Zuk hypothesis or the immunocompetence mechanism, but it does raise doubts about a widespread assumption that is commonly used to test these hypotheses: that sexual selection on signals of health implies the choice of mates with the fewest parasites. Immunity and parasites might play a fundamental role in many biological signaling systems, but viability-indicating traits are not necessarily parasite-load-indicating traits. Theory allows for the possibility that high-quality big signalers have greater health and more parasites than low-quality small signalers (and the data suggest that in many systems they do). This means that we cannot test the Hamilton-Zuk hypothesis or the immunocompetence handicap hypothesis by counting parasites. More generally, we cannot understand sexual selection on signals of health by focusing on the viability costs of signals.

Ancient origins of nitric oxide signaling in biological systems.

The simple gas nitric oxide (NO) controls a variety of complex biological processes, including blood pressure homeostasis, platelet aggregation, and transmission of signals by the nervous system. NO is also important for immune system function, playing key roles in the activation of macrophages and cellular defenses against microbial pathogens. Recent studies have revealed that some responses to NO are similar to those among very distantly related organisms; these findings suggest that many of the biological functions of NO have an evolutionarily ancient origin.

Complexity in biological signaling systems.

Biological signaling pathways interact with one another to form complex networks. Complexity arises from the large number of components, many with isoforms that have partially overlapping functions; from the connections among components; and from the spatial relationship between components. The origins of the complex behavior of signaling networks and analytical approaches to deal with the emergent complexity are discussed here.

Eicosanoids mediate insect cellular immune reactions to bacterial infections.

The occurrence of eicosanoids in invertebrate tissues has been recognized for nearly thirty years, beginning with the discovery of certain prostaglandins (PGs) in some species of octacorals1. This discovery attracted more commercial than zoological attention because the large amounts of PGs in the corals represented a natural source of material for research and other pharmaceutical interests2. The initial finding prompted efforts to locate other natural sources of PGs and other eicosanoids, and it is now commonly thought that eicosanoids occur in the tissues of virtually every animal taken under appropriate scrutiny. This idea carries considerable significance, because it suggests eicosanoids were recruited into biological signaling systems before evolution of the Metazoa. I suppose eicosanoids occur in most, if not all, animals, and eicosanoids exert important biological actions in animals. Some eicosanoid actions are limited to a few species. For example, PGs release egg-laying behavior in some, but not all, cricket species3. Similarly, F-series PGs serve as sex pheromone in some, by no means all, fish species4. On the other hand, other eicosanoid actions may be fundamental to animal systems. Eicosanoids seem to be involved in ion transport physiology in every vertebrate and invertebrate suitably studied5. Regulating ion transport physiology may be a fundamental eicosanoid action. In a similar vein, we will suggest in this chapter that mediating cellular defense reactions may also be a fundamental eicosanoid action.

Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model.

Paradoxically, nitric oxide (NO) has been found to exhibit cytotoxic, antiproliferative, or cytoprotective activity under different conditions. We have utilized Salmonella mutants deficient in antioxidant defenses or peptide transport to gain insights into NO actions. Comparison of three NO donor compounds reveals distinct and independent cellular responses associated with specific redox forms of NO. The peroxynitrite (OONO-) generator 3-morpholinosydnonimine hydrochloride mediates oxygen-dependent Salmonella killing, whereas S-nitrosoglutathione (GSNO) causes oxygen-independent cytostasis, and the NO. donor diethylenetriamine-nitric oxide adduct has no antibacterial activity. GSNO has the greatest activity for stationary cells, a characteristic relevant to latent or intracellular pathogens. Moreover, the cytostatic activity of GSNO may best correlate with antiproliferative or antimicrobial effects of NO, which are unassociated with overt cell injury. dpp mutants defective in active dipeptide transport are resistant to GSNO, implicating heterolytic NO+ transfer rather than homolytic NO. release in the mechanism of cytostasis. This transport system may provide a specific pathway for GSNO-mediated signaling in biological systems. The redox state and associated carrier molecules are critical determinants of NO activity.

Calpain: new perspectives in molecular diversity and physiological‐pathological involvement

Calpain, calcium-activated neutral protease, stands as a unique receptor for calcium signals in biological systems; its activation leads to irreversible proteolytic processing of substrate proteins, modifying cellular situations in a manner distinct from that of reversible processes including the phosphorylation-dephosphorylation reactions. Because the enzyme participates not only in normal intracellular signal transduction cascades but also in various pathological states including ischemia, calpain research has attracted tremendous interest in wide areas of life sciences in both basic and clinical terms. This review will address the new perspectives evoked by recent discoveries since 1990. Molecular biological studies have established that calpain in fact constitutes a large family of distinct isozymes differing in structure and distribution, whereas an increasing number of reports describe physiological-pathological involvement of calpain. Another major accomplishment is the technical breakthrough allowing spatial resolution of calpain action presenting a clearer in vivo picture of how calpain acts in cells and tissues.

The continuous Sir Philip Sidney game: A simple model of biological signalling

An analysis of Maynard Smith's two-player, ESS model of biological signalling, the "Sir Philip Sidney game", is presented. The stable strategies of the players in this game are shown to satisfy the conditions of Zahavi's handicap principle. At equilibrium, signals are honest, costly, and costly in a way that is related to the true quality revealed. Further analysis reveals that the level of cost required to maintain stability is inversely related to the degree of relatedness between the players. It therefore seems likely that stable biological signalling systems will feature lower signalling costs when communication occurs between relatives. A three-player, extended version of the model is investigated, in which signals are passed via an intermediate, or "messenger". It is shown that this destabilizes the signalling system, and leads to increased signalling costs. This result suggests that "kin conflict" theories of the evolution of the endosperm in flowering plants require further refinement. The introduction of a novel resource acquisition tissue, which mediates parent-offspring interaction during development, cannot be assumed to limit parent-offspring conflict simply because it carries an extra copy of the maternally inherited genes. The ability to add such complications to the Sir Philip Sidney game and still obtain solutions makes it a very useful modelling tool.

The Effect of Shape on the Surface-Volume Relationships of Birds' Eggs

THEORY Surface-volume relationships are of widespread functional significance in biological systems, and one might intuitively expect that shape would affect the surface-volume relationships of birds eggs. Besch et al. (1968) summarized the literature on the estimation of egg surface area and presented the details of an accurate new method for its measurement. Utilizing a semi-automated version of this method, Paganelli et al. (1974) conducted a comparative study of the surface areas and volumes of the eggs of 29 species of birds. The relationship between surface area and volume which they reported was: VOLUME AND SURFACE AREA

Nucleoside Antibiotics: I. BIOCHEMICAL TOOLS FOR STUDYING THE STRUCTURAL REQUIREMENTS FOR INTERACTION AT THE CATALYTIC AND REGULATORY SITES OF RIBONUCLEOTIDE REDUCTASE FROM LACTOBACILLUS LEICHMANNII

Abstract The structural requirements for reactivity at the substrate site and for interaction at the regulatory site of ribonucleotide reductase from Lactobacillus leichmannii have been studied with the use of several nucleotide antibiotics. The 5'-triphosphates of tubercidin, toyocamycin, and sangivamycin were substrates. Without Mg++, tubercidin 5'-triphosphate was a better substrate than ATP. Therefore, the imidazole ring of ATP can be replaced by the pyrrole ring. The presence of a hydroxyl group at position 3' is especially important for reduction since 3'-deoxyadenosine 5'-triphosphate was not a substrate. 3'-Deoxyadenosine 5'-triphosphate did inhibit reduction of ATP but did not compete for the reduction of UTP, GTP, or CTP. Modification of the reductase by the prime effectors, dGTP and 2'-dATP, stimulated the reduction of the 5'-triphosphates of tubercidin and toyocamycin. Reduction of sangivamycin 5'-triphosphate was stimulated by dGTP but not 2'-dATP. Although 3'-deoxyadenosine 5'-triphosphate was not a substrate, it was 50% as good an effector as 2'-dATP for stimulating the reduction of CTP. The pyrrolopyrimidine ribonucleotide antibiotics were less effective than 3'-deoxyadenosine 5'-triphosphate and the pyrazolopyrimidine ribonucleotide, formycin 5'-triphosphate, could not be substituted for ATP. Carbon atom 8 and nitrogen atom 9 of the base portion of ATP, but not nitrogen atom 7, are important for interaction at the regulatory site of ribonucleotide reductase, while a hydroxyl at position 3' of ribose is not essential. ATP, UTP, and GTP reductions are only slightly stimulated when the nucleotide antibiotics are added as allosteric effectors. The reduction of the nucleotide antibiotics and regulation of the reductase may be of possible significance in biological systems.