Endotoxin-like effects in acute phase response to Trypanosoma brucei brucei infection are not due to gastrointestinal leakage

Trypanosomosis is mainly an immunological and inflammatory response mediated by increased levels of pro-inflammatory cytokines. Evidence suggests that pathological changes produced during infection with trypanosomes could be initiated by nonspecific endotoxin-like substances in trypanosomes and/or Gram-negative secondary bacterial infection. Studies in trypanosome-infected rats indicate damage to the gastrointestinal tract (GIT) accompanied by increased leakage of the GIT mucosa. The current study was carried out to determine the in vivo response to endotoxin-like substances of Trypanosoma brucei brucei. To this purpose we neutralized the entrance of endotoxin through the GIT using polymyxin-B treatment and monitored the plasma concentration of the acute phase proteins SAP and Hp. The results in this study, where infection was performed in the presence of oral antibiotic that is not absorbed from GIT and which binds to and inactivates endotoxin, show that the elevated plasma levels of endotoxin-like activity and the resulting acute phase response indicated by an increase in levels of Hp and SAP, are due to trypanosome infection. Results obtained in the present study indicate that GIT is not the major source of elevated plasma endotoxin-like activity levels and the observed acute phase response was due to an increase in the levels of acute phase proteins SAP and haptoglobin.Therefore trypanosomes are responsible for the elevated plasma endotoxin-like activity levels and the subsequent systemic acute phase response in the host.     

Bacteriophage T4D Receptor and the Escherichia coli Cell Wall Structure: Binding of Endotoxin-Like Particles to the Cell Wall

A variety of degradative treatments have been used to investigate the nature of the structure and components of the cell walls of Escherichia coli B. The binding and localization of the endotoxin-like particles found on the cell walls were of special interest because some of them are associated with the site where the inner tail tube of bacteriophage T4D penetrates the cell wall. Modified cell walls were obtained by heating a suspension of bacterial cells originally in 0.1 M phosphate, pH 7.0, after the addition of 12.5 M NaOH to a final concentration of 0.25 M. With regard to the endotoxin-like particles, it was found that: (i) at least part of them still remained bound to the modified cell wall after the alkali treatment; (ii) the subsequent incubation of alkali-treated cell walls with lysozyme destroyed the bacterial form and released a complex of endotoxin-like particles together with a fibrous material; (iii) on the other hand, treatment with 45% phenol at 70°C removed the endotoxin-like particles from the surface of the alkali-treated cell walls, but most of the fibrous material was left on the cell wall; and (iv) incubation of alkali-treated cell walls with 5 mM ethylenediaminetetraacetic acid at 20°C also removed the endotoxin-like particles, but did not disrupt the rodlike bacterial form. However, if the ethylenediaminetetraacetic acid treatment was performed at 55°C, the bacterium-like form was destroyed. These differential sensitivities to ethylenediaminetetraacetic acid suggested that loosely bound divalent metal ions normally hold these endotoxin-like particles on the cell wall surface, but that probably more tightly bound metal ions are involved in the determination of cell shape. Analysis of the protein components of the alkalitreated cell walls showed that only one protein was present in significant amounts, and this protein had an electrophoretic mobility similar to that of the Braun lipoprotein. This protein was released from the alkali-treated cell walls upon heating with 2% sodium dodecyl sulfate at 100°C. Phospholipids were also absent from this structure. The distribution of the remaining cell wall components on the alkali-treated cell walls is discussed.     

The induction of tyrosine aminotransferase activity and its use as an indirect assay for endotoxin in mice infected with Plasmodium vinckei petteri

Gauci R., Bennett D., Clark I. A. and Bryant C. 1982. The induction of tyrosine aminotransferase activity and its use as an indirect assay for endotoxin in mice infected with Plasmodium vinckei petteri. International Journal for Parasitology12: 279–284. It has been suggested that the malaria parasite contains an endotoxin-like substance which, by activating the reticuloendothelial system, causes much of the pathology of malaria when it is released into the host bloodstream during schizogony. In this study, an in vivo assay was developed, based on the determination of hepatic tyrosine aminotransferase activity in infected mice, to measure substances which act like endotoxin. Tyrosine aminotransferase is important in gluconeogenesis and is induced by endotoxin. Mice infected with Plasmodium vinckei petteri become sensitised to bacterial endotoxin as small amounts of endotoxin, without effect in uninfected mice, elevate tyrosine aminotransferase activity. The increase in sensitivity is gradual and progressive and is detectable by day 2 of the 9 day infection. Tyrosine aminotransferase activity is first lowered and then raised markedly during the course of the disease. A cell-free preparation of malaria parasites increased tyrosine aminotransferase activity when injected into mice sensitised with Coxiella antigen. These results are consistent with the hypothesis that parasitised red cells contain an endotoxin-like substance which directly or indirectly may be responsible for producing some of the symptoms of malaria in mice.     

A new theory of infarction-genesis in cats

It can be shown that a number of substances that are derived from incubation have a good blocking capacity in myocardial infarction. There exists also a natural substance (intrinsic factor, i.f.) which can also block infarction. The same substances also inhibit arrhythmias of ischaemic origin. Thus a common root for myocardial infarction and arrhythmias could be inferred. A new dynamic method (T/2 velocity) was elaborated for evaluating anti-infarction drugs instead of using static T/2 values. Oxidation of i.f. in vitro and in vivo enhances the blocking capacity of artificial drugs reagented previously each other. The natural substance (i.f.) lost its blocking capacity after oxygenation, thus may be unable to compete with the above mentioned artificial substances. Ligation of the coronaries i.e. its myocardial infarction producing effect can also be inhibited by the same substances. No matter how infarction is produced, the same substances can block it. Since after cutting the vagi KCl elicits the same phenomena their reflex origin can be excluded.     

Endotoxin-like activities inMyxococcus xanthus

Vegetative cells as well myxospores ofMyxococcus xanthus have shown anticomplementary activity and the capacity to be used as active agents in the skin preparation of the Shwartzman reaction and in its intravenous induction. These endotoxin-like properties were not extractable by the hot phenol-water methods. Our results suggest the presence of a lipid A analog in both vegetative cells and myxospores, and emphasize the difficulty of lipopolysaccharide detection; this is perhaps a consequence of a developing associated change in polysaccharide moiety of the myxobacterial lipopolysaccharides; this may be the basis of the special immunomodulation pattern shown byM. xanthus myxospores.     

Heterogeneity of receptor immunoreactivity at synapses of glycine-utilizing neurons.

Neurons often contain, and probably release, more than one neuroactive substance that may have diverse or opposite actions on the postsynaptic cell. It remains unexplained how these neurons utilize their multiple neuroactive substances while maintaining appropriate resolution of neurotransmitter functions. Here, we have examined the ultrastructural localization of glycine receptors by using a monoclonal antibody directed to the intracellular domain of the strychnine-sensitive glycine receptor. We have found that glycine receptors are only localized to 56% of the synapses made by presumed 'glycinergic' (more accurately, glycine-utilizing) amacrine cells in the turtle retina. The remaining synapses made by these same boutons show no evidence of glycine receptors. As there is no evidence to suggest the presence of a second type of glycine receptor, these data indicate that only a portion of the postsynaptic sites contacted by the glycine-utilizing neurons can respond to glycine. They also suggest that a neuron containing multiple neuroactive substances can selectively affect postsynaptic elements by means of heterogeneous receptor localization.     

Interferons: Purification and Physicochemical Aspects

Antiviral interferon activity in any one species can be exhibited by a variety of substances that differ in their physical and chemical properties, but the nature of these differences is not understood. Conditions that can lead to the formation of diverse types of interferons have been outlined. Reasons have been adduced why, for certain purposes, purification of interferons is desirable or even necessary, and examples have been presented to show how and to what extent this has been achieved. In spite of some very high purification factors, not a single interferon has been obtained as a pure substance. Therefore, all available knowledge of physical and chemical properties has been obtained by indirect means.     

Diffusion within egg lecithin bilayers resembles that within soft polymers

An analysis is presented of how the permeability coefficient/octanol:water partition coefficient ratio for 33 different chemical substances crossing egg lecithin bilayers depends on the molecular volume of the substances. From this analysis we conclude that bilayers made from egg lecithin behave as soft polymers in their discrimination between permeants of different sizes and shapes.     

Host-parasite interactions from an ecotoxicological perspective

In recent years there has been an increasing number of papers showing how parasitism and pollution can interact with each other in aquatic organisms. Apart from parasitological aspects these interactions are also important in terms of ecotoxicological research. The current presentation aims at identifying three promising directions for future research in the interdisciplinary field of parasitology and ecotoxicology. 1. Parasites as sinks for pollutants within their hosts: Some parasites are able to reduce pollutant levels in the tissues of their host. The reduction of pollutants is an interesting implication since parasites are beneficial to their hosts from this perspective. In other cases free-living accumulation indicators may erroneously indicate low levels of pollution if they are infected with parasites. 2. Parasites as a diagnostic tool to test bioavailability of substances. In order to take up and accumulate pollutants the substances have to be metabolized by the host first. Accordingly, the detection of substances within endoparasites is a sign for the biological availability of pollutants. 3. Changes of biomarker responses of the host against pollutants. Parasites can alter physiological reactions of their hosts against pollutants in different ways. Therefore, in ecotoxicological studies, examining the question whether exposure to certain chemicals affects the physiological homeostasis of a test organism, it is important to use organisms that are known to be uninfected.     

Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells

Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing beta cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.     

Communication in bacteria: an ecological and evolutionary perspective

Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria.     

The expression of neuropeptide Y immunoreactivity in the avian sympathoadrenal system conforms with two models of coexpression development for neurons and chromaffin cells.

We have studied the expression and development of neuropeptide Y-like immunoreactivity (NPY-LI) in the sympathoadrenal system of the chicken using single and double immunocytochemical techniques and radioimmunoassay. NPY-LI is expressed by neurons of the paravertebral sympathetic ganglia and by chromaffin cells of the adrenal gland in embryonic and adult chickens. The peptide is coexpressed with catecholaminergic properties in neurons. In chromaffin cells, it is also expressed with immunoreactivity to somatostatin and serotonin. We have used the expression of NPY-LI to analyze how cells that coexpress two or more neuroactive substances arrive at their final phenotype. Our results suggest that the ontogeny of coexpression in neurons of the avian paravertebral sympathetic ganglia occurs in a sequential pattern, where the expression of the peptide follows the initial expression of the "classical neurotransmitter". In contrast, in chromaffin cells, expression of the peptides occurs concomitantly with expression of catecholaminergic properties or soon after. Initially, coexpression of several neuroactive substances occurs, but this is followed by further specialization where the expression of one peptide prevails over the other. We believe that the two models of coexpression shown by our results can be used to describe the ontogeny of coexpression in other cells of the nervous system.     

Interspecific variation in ejaculate allocation and associated effects on female fitness in seed beetles

When ejaculates are costly to produce, males are expected to allocate their ejaculate resources over successive matings in a manner that optimizes their reproductive success and this may have important consequences for their mates. In seed beetles (Coleoptera; Bruchidae), ejaculates vary in size across species from weighing less than 1%, up to as much as 8%, of male body weight. Ejaculates contain not only sperm but also a range of additional substances and females in some species gain benefits from receiving large ejaculates. Male ejaculate allocation may thus affect female fitness. Here, we first characterized the pattern of male ejaculate allocation over successive matings in seven-seed beetle species. We then assessed how this allocation affected female fitness in each species. Although females generally benefited from receiving large ejaculates, the interspecific variation observed both in ejaculate allocation patterns and in their effects on female fitness was remarkably large considering that the species studied are closely related. Our analyses suggest that variation in ejaculate composition is the key, both within and across species. We discuss possible causes for this variation and conclude that coevolution between male ejaculates and female utilization of ejaculate substances has apparently been rapid in this clade.     

药用植物内生真菌及活性物质多样性研究进展

药用植物具有丰富的物种多样性,是人类生存与发展的重要自然资源。内生真菌广泛存在于健康植物组织内部,是植物微生态系统的重要组成部分,各种药用植物中蕴藏着非常丰富的内生真菌。通过与药用植物的“协同进化”,某些内生真菌具有了产生与宿主植物相同或相似的生物活性物质的能力。内生真菌产生的各种活性物质,在生物制药、农业生产、工业发酵等方面都表现出美好的应用前景,受到世界各国专家的广泛关注。利用内生真菌发酵实现生物活性物质的工业化生产,可以提高产量、降低产品成本,满足人们日益增长的需求;同时有利于珍稀、濒危药用植物资源的保护,对减少野生药用植物多样性的破坏具有重要意义。本文从药用植物内生真菌物种多样性与产生生物活性物质多样性等方面总结近年最新的研究进展,提出了内生真菌及活性物质研究的未来发展方向。     

Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors

To secure their access to water, light, and nutrients, many plant species have developed allelopathic strategies to suppress competitors. To this end, they release into the rhizosphere phytotoxic substances that inhibit the germination and growth of neighbors. Despite the importance of allelopathy in shaping natural plant communities and for agricultural production, the underlying molecular mechanisms are largely unknown. Here, we report that allelochemicals derived from the common class of cyclic hydroxamic acid root exudates directly affect the chromatin-modifying machinery in Arabidopsis thaliana. These allelochemicals inhibit histone deacetylases both in vitro and in vivo and exert their activity through locus-specific alterations of histone acetylation and associated gene expression. Our multilevel analysis collectively shows how plant-plant interactions interfere with a fundamental cellular process, histone acetylation, by targeting an evolutionarily highly conserved class of enzymes.     

Yolk androgens as pleiotropic mediators of physiological processes: a mechanistic review

Avian egg yolks are made up of complex mixtures of physiologically relevant substances. Androgens, in particular, accumulate in yolks in variable amounts based on social and environmental conditions experienced by laying females, and using experimental elevations of yolk androgen content, researchers have unveiled potent physiological and behavioral effects on offspring. These patterns and effects are exciting in an adaptive context, as the transfer of endogenously-produced substances such as androgens to egg yolks may allow fine manipulation of offspring phenotype to maximize reproductive success. However, to gain an in-depth understanding of how yolk androgens function in an adaptive context, we must first understand the complex entanglement of physiological and endocrine interrelationships that change after exposure to yolk androgens. Here, we take a comparative approach towards a discussion of how yolk androgens can simultaneously affect multiple body systems within developing birds, ultimately resulting in the large-scale phenotypic endpoints that may represent adaptive consequences of exposure to elevated levels of yolk androgens.     

Different effects of paternal trans-generational immune priming on survival and immunity in step and genetic offspring

Paternal trans-generational immune priming, whereby fathers provide immune protection to offspring, has been demonstrated in the red flour beetle Tribolium castaneum exposed to the insect pathogen Bacillus thuringiensis. It is currently unclear how such protection is transferred, as in contrast to mothers, fathers do not directly provide offspring with a large amount of substances. In addition to sperm, male flour beetles transfer seminal fluids in a spermatophore to females during copulation. Depending on whether paternal trans-generational immune priming is mediated by sperm or seminal fluids, it is expected to either affect only the genetic offspring of a male, or also their step offspring that are sired by another male. We therefore conducted a double-mating experiment and found that only the genetic offspring of an immune primed male show enhanced survival upon bacterial challenge, while phenoloxidase activity, an important insect immune trait, and the expression of the immune receptor PGRP were increased in all offspring. This indicates that information leading to enhanced survival upon pathogen exposure is transferred via sperm, and thus potentially constitutes an epigenetic effect, whereas substances transferred with the seminal fluid could have an additional influence on offspring immune traits and immunological alertness.     

Inhibition of female mating by male accessory gland substances in the ground beetle Leptocarabus procerulus

The ground beetle Leptocarabus procerulus (Chaudoir) possesses seminal substances that have a physical function to form mating plugs and a physiological function to induce female refractory behaviour, which act together to hinder female remating. Little is known about the physiological properties of the substances inducing female refractory behaviour, especially with respect to their secretory organ, dose‐dependency, molecular characteristics and the effect of female maturity. By injecting male‐derived substances into females, substances that induce female refractory behaviour are shown to be produced in the male accessory gland but not in the testis. Injection of extracts from the accessory gland increases the female refractory period at moderate doses but not at lower or higher doses. By contrast, injection of extracts from the testis reduces the female refractory period at high doses. The lack of an effect of accessory gland substances at higher doses could be the result of an anomalous effect of unnaturally large doses of seminal products by direct injection, the toxicity of seminal substances that deter female responses, or counteraction by injected substances that promote female receptivity. The accessory gland substances lose their activity when heated, although the testis substances do not. Females without mature eggs tend to reject mating entirely, although variation in the number of mature eggs (one or more) is not associated with the female refractory period, indicating the limited effect of female reproductive maturity. These findings may help to clarify the physiological basis of the evolution of the elaborated male mating behaviour in L. procerulus.     

The role of endogenous bioregulators in formation of cardiogenic reflex effects on circulation

The possible role of endogenous endothelium-derived bioactive substances in organization of cardiogenic depressor reflexes under cardiac receptor stimulation (by veratrine and bradykinin) was investigated in acute experiments on anesthetized rats. The results have shown that endothelium-derived bioactive substances take part in forming of the cardiogenic depressor reflex humoral components of nervous response or nervous modulators. These data contribute to understanding of the role of endogenous endothelium-derived bioactive substances (prostacyclin) and different NOS isoforms in mechanisms of depressor reflex development and species differences in their involvement in reflex vasomotor reactions.