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At least 19 recordsLinked to original sources
PubMed2025

Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity.

Catalysis and specifically autocatalysis are the quintessential building blocks of life. Yet, although autocatalytic networks are necessary, they are not sufficient for the emergence of life-like properties, such as replication and adaptation. The ultimate and potentially fatal threat faced by molecular replicators is parasitism; if the polymerase error rate exceeds a critical threshold, even the fittest molecular species will disappear. Here we have developed an autocatalytic RNA early life mathematical network model based on enzyme kinetics, specifically the steady-state approximation. We confirm previous models showing that these second-order autocatalytic cycles are sustainable, provided there is a sufficient nucleotide pool. However, molecular parasites become untenable unless they sequentially degenerate to hyperparasites (i.e. parasites of parasites). Parasite resistance-a parasite-specific host response decreasing parasite fitness-is acquired gradually, and eventually involves an increased binding affinity of hyperparasites for parasites. Our model is supported at three levels; firstly, ribozyme polymerases display Michaelis-Menten saturation kinetics and comply with the steady-state approximation. Secondly, ribozyme polymerases are capable of sustainable auto-amplification and of surmounting the fatal error threshold. Thirdly, with growing sequence divergence of host and parasite catalysts, the probability of self-binding is expected to increase and the trend towards cross-reactivity to diminish. Our model predicts that primordial host-RNA populations evolved via an arms race towards a host-parasite-hyperparasite catalyst trio that conferred parasite resistance within an RNA replicator niche. While molecular parasites have traditionally been viewed as a nuisance, our model argues for their integration into the host habitat rather than their separation. It adds another mechanism-with biochemical precision-by which parasitism can be tamed and offers an attractive explanation for the universal coexistence of catalyst trios within prokaryotes and the virosphere, heralding the birth of a primitive molecular immunity.

Kinetics↗
PubMed1992

The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections.

Parasite-exposed lambs and their parasite-naive controls were experimentally infected once only with 30,000 H. contortus larvae at 3, 9, 12, and 20 weeks following termination of a moderate immunizing infection of 30,000 H. contortus larvae. Previously exposed lambs, challenged at 3 weeks, had a significant reduction in the total H. contortus worm burden as compared to parasite-naive controls. No difference in the total H. contortus worm burden was found between parasite-exposed or parasite-naive lambs challenged at 9 weeks or thereafter. Female worms were found to be significantly smaller in lambs previously exposed to the parasite as compared to those found in parasite-naive lambs. The average parasite fecundity was 4700 eggs per female worm per day. Previous exposure of the lambs to the parasite had no effect on parasite fecundity. Various mathematical models were used to examine parasite fecundity. Parasite fecundity was found to increase in the initial post-challenge period reaching a constant value approximately 58 days after challenge infection. No density-dependent constraints on fecundity were observed.

Animals↗
PubMed1991

Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability.

In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium-dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm.

Animals↗
PubMed1992

An hypothesis to explain why cell-mediated immunity alone can contain infections by certain intracellular parasites and how immune class regulation of the response against such parasites can be subverted.

Cells with a low density of parasite-specific antigens on their surface are postulated to be susceptible to a cell-mediated attack but not to effector mechanisms normally activated following the binding of specific antibody to the infected cell. It is further postulated that such infected cells normally induce a cell-mediated response, and that cells infected with slow-growing intracellular parasites have a low density of parasite-specific antigens on their surface. Despite these general postulates, cell-mediated immunity is not invariably induced following natural infection by certain slow-growing parasites, such as those responsible for leprosy, tuberculosis, and the leishmaniases, and antibody can be induced that is exclusive of a strong, cell-mediated response. It is proposed that certain events in such cases subvert the normal regulatory processes that control the class of immunity induced. In these cases, the parasite-infected cells, bearing a low representation of parasite antigens, induce antibody even though they are not susceptible to antibody-dependent effector mechanisms, and so they are not eliminated. In this case, chronic infection and uncontrolled growth of the parasite occurs, often with fatal consequences.

Animals↗
PubMed1990

Genetic complexity of Plasmodium vivax parasites in individual human infections analyzed with monoclonal antibodies against variant epitopes on a single parasite protein.

Monoclonal antibodies against variant epitopes of a highly polymorphic protein (PV200) in schizonts of Plasmodium vivax have been used to analyze the variety of genetically distinct populations of parasites present in the peripheral blood of individual P. vivax infections in Sri Lanka. In 9 out of 10 isolates of freshly drawn P. vivax infected blood from different individuals, parasites of only 1 PV200 serotype was found within each individual infection, even though parasites were serotypically distinct between individuals. In 1 isolate parasite population, 3 distinct PV200 serotypes were identified. Thus, most P. vivax infections appeared to consist of a single genetically homogeneous population of parasites within the detection limits of the technique. The prevalence of P. vivax infections in an area of malaria transmission in southern Sri Lanka and the densities of oocysts in mosquitoes fed on P. vivax infected individuals indicated that parasite populations would be transmitted many times before encountering parasites of other origins, and that individual populations would tend to reduce to genetic homogeneity during transmission. These expectations are consistent with the high proportion of genetically homogeneous P. vivax isolates observed.

Adult↗
PubMed1991

Circumsporozoite protein gene from Plasmodium reichenowi, a chimpanzee malaria parasite evolutionarily related to the human malaria parasite Plasmodium falciparum.

We have cloned and sequenced the gene encoding the circumsporozoite (CS) protein of Plasmodium reichenowi a Plasmodium falciparum-like malaria parasite of chimpanzees. Comparison of the two CS proteins reveals both similarities and differences in these two evolutionarily related parasites that have adapted to different hosts. The P. reichenowi CS protein has a new repeat sequence, NVNP, in addition to the P. falciparum-like NANP and NVDP repeats. In the immunodominant TH2R and TH3R regions of the CS protein, the amino acid sequences are similar in both parasite proteins. The differences in the two proteins exist in domains around the conserved regions, Region I and Region II, which are otherwise conserved in the CS proteins of P. falciparum analyzed to date. Studies of parasite protein genes of evolutionarily related malaria parasites, together with other immunologic and biologic characteristics, will help better understand the evolution and host parasite relationship of malaria parasites and may provide a tool for identifying protein determinants for malaria vaccine development.

Amino Acid Sequence↗
PubMed1975

Parasite reproductive strategy and evolution of castration of hosts by parasites.

A modification of the Euler equation is used to describe a simple parasite life history in which survival decreases with age at a rate determined by mortality of the parasitized host. The advantages of castration of hosts by parasites are discussed using the modified equation in which castration is equivalent to reducing parasite virulence in the host to near zero or zero. It is suggested that castrating parasites can infest a wider range of hosts with higher mortality rates and that within parasite groups having castrating and noncastrating species, the former should infest hosts with higher mortality rates and relatively larger gonads.

Ecology↗
PubMed1978

The effect of variations in host and parasite density on the level of parasitization of Lymnaea truncatula by Fasciola hepatica.

Groups of the snail Lymnaea truncatula, maintained at a range of spatial densities, were exposed to different densities of miracidia of Fasiola hepatica. The resulting degree of parasitization was measured 3--4 weeks after infection. The relationship between parasite densities and parasitization appeared to be curvilinear. The lower than expected parasitization at high parasite densities could be explained by the multiple infection of some snails by two or more miracidia. The level of parasitization was not related exponentially to the temperature at which infection was carried out. This was thought to be due to the inverse relationship between miracidial longevity and swimming speed, with respect to temperature. A depth of free water overlying a mud surface was an absolute requirement for miracidia to successfully infect snails.

Animals↗
PubMed1992

Niche breadth in parasites: an evolutionarily stable strategy model, with special reference to the protozoan parasite Leishmania.

A parasite's host range essentially defines its niche breadth, which, as foraging theory predicts, is influenced by resource availability. For parasites, the interaction of infection and transmission characteristics with host population dynamics determines host availability. An epidemiological model, involving two host types and describing competition between a "generalist" parasite strain and a related "specialist" strain, is used to examine the interplay among host range, relative host availabilities, and adaptational compromises engendered by increased host range. Results show that the generalist can predominate even when it cannot maintain itself in either host alone, but that the specialist can persist if its reproductive rate attains some threshold relative to either of the generalist's respective rates in its two hosts. The model is in rough, qualitative agreement with observed dynamics of two Leishmania parasite-host systems, and overall results suggest that infection of two species with a common parasite can lead to complex, indirect coevolutionary dynamics.

Adaptation, Biological↗
PubMed1991

Sexual showiness and parasite load: correlations without parasite coevolutionary cycles.

Hamilton & Zuk (1982, Science 218, 384-387.) produced a model of sexual selection in which coevolutionary cycles of host and parasites generate consistently positive correlations between parent and offspring viability, and that animals choose mates for genetic disease resistance by scrutinizing characters whose full expression is dependent on health and vigour. They predicted a positive correlation between sexual showiness and parasite burden across species, and a negative correlation within a species. First, recent suggestions that interspecific correlations in the opposite direction to that indicated above are consistent with the mechanisms of Hamilton & Zuk's model are discussed. Second, it is shown that the model's predictions can be produced by heritable variation maintained by non-parasite fluctuating selection. In this case, the parasites associated with degree of sexual showiness are those able to amplify any initial heritable differences in vigour. Alternative sources of positive correlation between parent and offspring viability, which include the indirect effects of climatic change and exclude the need for host-parasite coevolutionary cycles, are also proposed.

Animals↗
PubMed1975

[Glutathionestatus of Plasmodium vinckei parasitized erythrocytes in correlation to the intraerythrocytic development of the parasite (author's transl)].

The glutathione status of Plasmodium vinckei parasitized erythrocytes of mice was determined in correlation to the intraerythrocytic stage of maturation of the parasite. The different stages of blood schizogony were separated by discontinuous Dextran-density-centrifugation. The changes of protein content, glutathione concentration (reduced/oxidized and bound/free glutathione) and in the specific activities of the following enzymes: gamma-glutamyl-cysteine-synthetase (GC-synthetase), glutathione-reductase (GR), glucose-6-phosphate dehydrogenase (Gl-DH), glutathione-peroxydase (G-POD) and catalase were investigated in dependence of the intraerythrocytic stage of development. The following changes of the investigated metabolic parameters were observed during the schizogony: - the protein content decreased to about one half, - the glutathione concentration increased about 10-fold, while the relations reduced/oxidized and free/bound glutathione remained constant, - Gl-DH activity appeared and increased steeply, - the specific activities of GC-synthetase and of GR increased more than 2-fold, while G-POD remained almost constant, - and the activities of G-6-PDH and catalase showed a significant, strong decrease to about 25% of the original values. It is tried to relate the observed changes to the growing parasite or to the host cell. The significance of the results for the metabolism of malaria parasites and for a possible adaptation to the mosquito by a GSH mediated protection of the malaria parasite against an enzymatic defence-reaction of the mosquito, is discussed.

Animals↗
PubMed1992

[Natural parasitism of buffaloes in Botucatu, SP, Brazil. III. Dynamics of gastrointestinal parasitism in cows and their calves].

Gastrointestinal parasitism of 24 buffalo cows before parturition, and post-parturition, their infection and that of their respective calves during the following 30 weeks were studied. Willis, Hoffmann and whenever possible, the modified Gordon & Whitlock techniques were used for fecal examinations. Toxocara vitulorum eggs were the earliest forms encountered in calves feces, as follows: during the 1st week after birth, 58.33% of the calves were positive, and in the 4th week, 100% of these animals were positive. Eggs of Strongyloides sp were in the 1st week after birth in two of the calves and in the 5th week, all for them were positive. The next parasites to appear were the Coccidia of which oocysts were detected in the feces of two calves in the 2nd week after birth, and 58.33% of the calves were positive for these in the 3rd week, and in the 6th week, all calves shed oocysts in their feces. On the other hand, eggs of Strongyloides were the last forms to appear in calves feces. However, despite their sporadic appearance in the feces, eggs of these parasites were observed continuously from the 11th week onwards, and at this point, the percentage of positive samples began to increase to reach its peak. Relatively to adult animals, eggs of T. vitulorum were observed in the feces of 11 cows, one or twice at most; eggs of Strongyloides sp were seen only once in the feces of four buffalo cows and eggs of Strongyloides in 21 out of 24 cows. Oocysts of Coccidia were observed in 16 cows. Mechanisms of infestation of calves with these parasites are discussed.

Animals↗
PubMed1991

Animal models in the study of the phenomenon of parasitism: filariae and other parasites.

The Round table has emphasized the absolute necessity of in vivo research showing the complexity of host reaction to the parasite. The results obtained in vitro can only provide a preliminary indication, because any interference with the culture is susceptible of changing the precarious balance of the parasite in that artificial environment. The subject proposed here cannot be treated wholly, but some particular topics could be discussed: 1--searching for appropriate models; 2--parasite strains; 3--some aspects on pathology and drug development; 4--vaccines; what significance in a natural host-parasite relationship can be gathered from a non-natural one?

Animals↗
PubMed1992

[The prevalence of intestinal parasites in primary school students in Trabzon and the importance of education of parasite patients].

Hundred and forty stool samples obtained from fourth classes (10 years of age) of the primary school students were examined for intestinal parasites. In addition, effect of education and variety of education on parasitic diseases were investigated. Of the 140 students 65% were found to be positive for intestinal parasites. Ascaris lumbricoides 15.7%, Trichuris trichiura 22.85%, Giardia intestinalis 7.14%, Ascaris lumbricoides + Trichuris trichiura 15.7%, Giardia intestinalis + Trichuris trichiura 3.57% were found. The infested students were treated with antiparasitic drugs, and were educated for parasitic diseases. 50% of the student were given brochure, the others were given brochure and verbal education. After 1.5 month control stool samples were taken. In both groups infestation rate was 27.14%. Ration was 18.57% in only brochure given group, and 8.57% in brochure and verbal education given group. The difference between two group was meaningful (X2 = 3.89 P less than 0.05).

Ascariasis↗
PubMed1978

[Parasites of Salmo trutta L. from the Tirino River. II. Host-parasite interactions of helminth species].

The hundred and sixteen brown trout (Salmo trutta L.) which were examined for helminth parasites were captured in the River Tirino, (L'Acquila - Italy). Six parasite species (Phyllodistomum simile, Crowcrocaecum testiobliquum, Crepidostomum metoecus, Cyathocephalus truncatus, Truttaedacnitis truttae and Dentitruncus truttae) were recovered. Ecological studies on each helminth species recovered have been carried out analysing the following aspects; the preference of each parasite species for certain microhabitats in the host; the incidence and intensity of each parasitic infection according to sex, age and season.

Age Factors↗
PubMed1992

Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.

The nematode parasites that cause human lymphatic filariasis survive for long periods in their vascular habitats despite continual exposure to host cells. Platelets do not adhere to blood-borne microfilariae, and thrombo-occlusive phenomena are not observed in patients with circulating microfilariae. We studied the ability of microfilariae to inhibit human platelet aggregation in vitro. Brugia malayi microfilariae incubated with human platelets caused dose-dependent inhibition of agonist-induced platelet aggregation, thromboxane generation, and serotonin release. As few as one microfilaria per 10(4) platelets completely inhibited aggregation of platelets induced by thrombin, collagen, arachidonic acid, or ionophore A23187. Microfilariae also inhibited aggregation of platelets in platelet-rich plasma stimulated by ADP, compound U46619, or platelet-activating factor. The inhibition required intimate proximity but not direct contact between parasites and platelets, and was mediated by parasite-derived soluble factors of low (less than 1,000 Mr) molecular weight that were labile in aqueous media and caused an elevation of platelet cAMP. Prior treatment of microfilariae with pharmacologic inhibitors of cyclooxygenase decreased both parasite release of prostacyclin and PGE2 and microfilarial inhibition of platelet aggregation. These results indicate that microfilariae inhibit platelet aggregation, via mechanisms that may include the elaboration of anti-aggregatory eicosanoids.

Animals↗
PubMed1990

[Characteristics of helminthic parasitism in cattle in Ituri (Haut-Zaire). II. Parasitic associations].

A total of 781 cattle was examined at the Bunia slaughterhouse (Ituri) from August 1986 to December 1987 to study the following parasitic associations: Fasciola sp., Schistosoma sp., paramphistomes and Fasciola sp., Haemonchus sp., Oesophagostomum sp. Prevalences were high for each parasite: 96.5% for paramphistomes, 58.1% for Schistosoma sp., 58.7 to 61.9% for Fasciola sp., 90.5% for Haemonchus sp. and 75.5% for Oesophagostomum sp. Regarding the association with trematodes, 41.3% of the 516 examined animals were simultaneously positive for the three helminths and there was a significant relationship between the infection with Fasciola sp. and Schistosoma sp. Regarding the association with Fasciola sp., Haemonchus sp. and Oesophagostomum sp., a total of 44.5% of the 265 examined animals harboured the three parasites together, but infections seemed not to be linked. Moreover, the corresponding gross lesions were moderate suggesting a low level of the parasitic burdens.

Animals↗
PubMed1991

Longitudinal study of young children in Kenya: intestinal parasitic infection with special reference to Giardia lamblia, its prevalence, incidence and duration, and its association with diarrhoea and with other parasites.

84 young children from a rural community, Nderu, in Kenya, were each followed for up to 10 months, from January to November 1987. Their ages ranged from 10 to 28 months over the period of study. Stools were obtained once a week, as were reports from the mothers about presence of abdominal complaints, including diarrhoea. A total of 2258 stools and 1873 reports were collected. 9 parasites were commonly encountered of which Giardia lamblia was the most frequent at 44.7%. The overall estimated number of new Giardia episodes per year per child was 2.77 +/- 2.22 SD and the mean estimated duration of infection was 75.25 +/- 73.84 SD days per child. The mean proportion of positive visits per child was 0.42 +/- 0.25 SD. Giardia trophozoites, Trichomonas hominis, Chilomastix mesnili, Entamoeba histolytica, Blastocystis hominis and Hymenolepis nana were all significantly associated with unformed stools and reports of diarrhoea. There was a significant probability of finding Giardia in stool within +/- 2 weeks of a report of diarrhoea. Poly-parasitism was common and several paired associations were significantly positive, particularly between species of amoebae. Quantity of Giardia in stool (expressed as a 0 to 5+ score) was suppressed both by type and number of other parasites present.

Age Factors↗