Liver fluke vaccines: Vaccination Against Fasciolosis by a Multivalent Vaccine of Recombinant Stage-Specific Antigens

Fasciola\u27s excretory-secretory material comprises chiefly cathepsin B and cathepsin L. These cysteine proteases are proposed as major mediators of parasitism, and are considered targets for vaccination. In order to assess the vaccine efficacy of these enzymes, single and multivalent recombinant protein vaccinations of adult-stage F. hepatica cathepsin L5, metacercarial-stage F. gigantica cathepsin L1 g and juvenile-stage F. hepatica cathepsin B were analysed in rats against F. hepatica challenge infection. The protective efficacy of anti-fluke vaccines was evaluated in terms of parasitological parameters (recovered fluke burden, fluke body size and wet weight) and pathological changes (liver damage score) in rats. The rats vaccinated with recombinant proteins were shown to have significantly fewer and smaller flukes than the control rats. A maximum protection of 83% was seen in the group vaccinated with a combination of cathepsin B and cathepsin L5

The effect of the liver fluke Fasciola gigantica infestation on the leucocyte eosinophil cell profile on sheep

Eosinophil is one of the major leucocyte cell in the blood which specifically reacted on parasite infection, thus it is important to determine its profile against the F. gigantica infection. The aims of this study is to determine the differences of the eosinophil count profiles on the different breed of sheep infected with F. gigantica and its relation with the resistance of sheep bred against parasitic disease. Four groups of sheep consist of Indonesian Thin Tail (ITT) sheep, Merino sheep, backcross sheep (10 families) and F2 sheep were infected with 300 metacercariae of Fasciola gigantica. The total sheep used in this trial is 621. Those sheep were observed for 12 weeks and the blood samples were collected every 2 weeks after infection. The results showed that total eosinophil counts in all infected sheep increased after two weeks post infection and ITT sheep showed the highest counts. On the other hand, the mean fluke counts on ITT sheep is the lowest compared with the other groups of sheep. Merino and F2 sheep had the highest mean fluke counts. Three families of backcross sheep had the mean flukes count similar to ITT sheep and the other 7 families were similar to the Merino sheep. In conclusion, the highest total eosinophil count at the early stage of infection on ITT sheep might be related with the genetic resistance, which was showed by the lowest flukes count, and the resistance was inherited to some of the backcross sheep, which had similar flukes count with ITT sheep.   Key words: Fasciola gigantica, eosinophil, shee

In vitro studies: The role of immunological cells in Indonesian thin tail sheep in the killing of the liver fluke, Fasciola gigantica

Previous studies have shown that Indonesian Thin Tail (ET) sheep exhibit high resistance to challenge with Fasciola gigantica when compared with Merino sheep, and this resistance is expressed in early infection. In order to study the role of the immune system in this resistance to ET sheep, in vitro studies were undertaken in the laboratory. In vitro study to confirm the ability of immune cells from ET sheep in the killing of F. gigantica larvae has been done by incubating immune cells and F. gigantica larvae together with immune sera or normal sera. The viability of the larvae was observed over a period 3 days incubation by observing their motility. The results showed that the cells isolated from F. gigantica- challenged ET sheep in the presence of immune sera from ET were able to kill 70% of the larvae. In contrast, cells from infected Merino were unable to kill a significant number of F. gigantica using the same sera source. It seems that the cytotoxicity was dependent on the presence of immune sera and ET peritoneal cells, suggesting the potential role of an antibody-dependent cell cytotoxic (ADCC) mechanism in the resistant ET sheep.Key words: In vitro, Fasciola gigantica, peritoneal cell, sheep gigantica

The U(1)-Higgs Model: Critical Behaviour in the Confinig-Higgs region

We study numerically the critical properties of the U(1)-Higgs lattice model, with fixed Higgs modulus, in the region of small gauge coupling where the Higgs and Confining phases merge. We find evidence of a first order transition line that ends in a second order point. By means of a rotation in parameter space we introduce thermodynamic magnitudes and critical exponents in close resemblance with simple models that show analogous critical behaviour. The measured data allow us to fit the critical exponents finding values in agreement with the mean field prediction. The location of the critical point and the slope of the first order line are accurately given.Comment: 21 text pages. 12 postscript figures available on reques

The responses of eosinophil and packed cell volume (PCV) on sheep infected with Fasciola gigantica

The responses of eosinophil and packed cell volume (PCV) values were verified in infected sheep, in order to identify whether these parameters could be used to predict the flukes burden and their correlation with breed resistance. Fifteen Indonesian thin tail sheep (ET), 9 Merino sheep and 148 backcross sheep generated from mating of Merino sheep and F1 sheep (Merino X ET cross) were infected with 300 metacercariae of Fasciola gigantica. The blood samples were collected every 2 weeks by using EDTA venoject tubes in order to determine the amount of eosinophils and the PCV value. After 14 weeks of infection all of sheep were killed and the liver was collected in order to determine the number of flukes. The results showed that the amount of eosinophils increased 2 weeks after infection and reached the peak at week 4 after infection. The average of eosinophils in ET appeared higher than the other 2 breeds (Merino was the lowest and the backcross was in between). The correlation between the number of flukes recovered from the liver and the eosinophil counts were positive in ET and Merino, but negative in the backcross sheep. The PCV values remained constant along the trial, except at week 14 after infection; the PCV values were slightly decreased in backcross sheep and Merino sheep, but not in ET sheep. The correlation between number of flukes in the liver and the PCV values were negative in all breeds of sheep. These results suggested that the eosinophilic and PCV’s response of ET were higher compared to backcross and Merino sheep, thus that responses were thought to be associated with the resistant phenomenon.   Key words: Fasciolosis, eosinophil, PCV, shee

Carcass conformation and fat cover scores in beef cattle: A comparison of threshold linear models vs grouped data models

Background: Beef carcass conformation and fat cover scores are measured by subjective grading performed by trained technicians. The discrete nature of these scores is taken into account in genetic evaluations using a threshold model, which assumes an underlying continuous distribution called liability that can be modelled by different methods. Methods: Five threshold models were compared in this study: three threshold linear models, one including slaughterhouse and sex effects, along with other systematic effects, with homogeneous thresholds and two extensions with heterogeneous thresholds that vary across slaughterhouses and across slaughterhouse and sex and a generalised linear model with reverse extreme value errors. For this last model, the underlying variable followed a Weibull distribution and was both a log-linear model and a grouped data model. The fifth model was an extension of grouped data models with score-dependent effects in order to allow for heterogeneous thresholds that vary across slaughterhouse and sex. Goodness-of-fit of these models was tested using the bootstrap methodology. Field data included 2,539 carcasses of the Bruna dels Pirineus beef cattle breed. Results: Differences in carcass conformation and fat cover scores among slaughterhouses could not be totally captured by a systematic slaughterhouse effect, as fitted in the threshold linear model with homogeneous thresholds, and different thresholds per slaughterhouse were estimated using a slaughterhouse-specific threshold model. This model fixed most of the deficiencies when stratification by slaughterhouse was done, but it still failed to correctly fit frequencies stratified by sex, especially for fat cover, as 5 of the 8 current percentages were not included within the bootstrap interval. This indicates that scoring varied with sex and a specific sex per slaughterhouse threshold linear model should be used in order to guarantee the goodness-of-fit of the genetic evaluation model. This was also observed in grouped data models that avoided fitting deficiencies when slaughterhouse and sex effects were score-dependent. Conclusions: Both threshold linear models and grouped data models can guarantee the goodness-of-fit of the genetic evaluation for carcass conformation and fat cover, but our results highlight the need for specific thresholds by sex and slaughterhouse in order to avoid fitting deficiencies

The origin of large molecules in primordial autocatalytic reaction networks

Large molecules such as proteins and nucleic acids are crucial for life, yet their primordial origin remains a major puzzle. The production of large molecules, as we know it today, requires good catalysts, and the only good catalysts we know that can accomplish this task consist of large molecules. Thus the origin of large molecules is a chicken and egg problem in chemistry. Here we present a mechanism, based on autocatalytic sets (ACSs), that is a possible solution to this problem. We discuss a mathematical model describing the population dynamics of molecules in a stylized but prebiotically plausible chemistry. Large molecules can be produced in this chemistry by the coalescing of smaller ones, with the smallest molecules, the `food set', being buffered. Some of the reactions can be catalyzed by molecules within the chemistry with varying catalytic strengths. Normally the concentrations of large molecules in such a scenario are very small, diminishing exponentially with their size. ACSs, if present in the catalytic network, can focus the resources of the system into a sparse set of molecules. ACSs can produce a bistability in the population dynamics and, in particular, steady states wherein the ACS molecules dominate the population. However to reach these steady states from initial conditions that contain only the food set typically requires very large catalytic strengths, growing exponentially with the size of the catalyst molecule. We present a solution to this problem by studying `nested ACSs', a structure in which a small ACS is connected to a larger one and reinforces it. We show that when the network contains a cascade of nested ACSs with the catalytic strengths of molecules increasing gradually with their size (e.g., as a power law), a sparse subset of molecules including some very large molecules can come to dominate the system.Comment: 49 pages, 17 figures including supporting informatio

Oxidative Modifications of Rat Liver Cell Components During Fasciola hepatica Infection

The aim of this paper was to assess the influence of Fasciola hepatica infection on oxidative modifications of rat liver cell components such as proteins and lipids. Wistar rats were infected per os with 30 metacercariae of F. hepatica. Activities and concentrations of liver damage markers were determined in the 4th, 7th, and 10th week postinfection (wpi). A decrease in antioxidant capacity of the host liver, manifested by a decrease in total antioxidant status (TAS), was observed. Diminution of antioxidant abilities resulted in enhanced oxidative modifications of lipids and proteins. F. hepatica infection enhanced lipid peroxidation, which was visible in the statistically significant increase in the level of different lipid peroxidation products such as conjugated dienes (CDs), lipid hydroperoxides (LOOHs), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The level of protein modification markers in the rat liver was also significantly changed and the most intensified changes were observed at seventh week postinfection. Concentration of carbonyl groups and dityrosine was significantly increased, whereas the level of tryptophan and sulfhydryl and amino groups was decreased. Changes in the antioxidant abilities of the liver and in the lipid and protein structure of the cell components resulted in destruction of the function of the liver. F. hepatica infection was accompanied by raising serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage. A significant decrease in lysosomal as well as in the total activity of cathepsin B during fasciolosis was also observed

Connectedness among herds of beef cattle bred under natural service

Background: A procedure to measure connectedness among herds was applied to a beef cattle population bred by natural service. It consists of two steps: (a) computing coefficients of determination (CDs) of comparisons among herds; and (b) building sets of connected herds. Methods: The CDs of comparisons among herds were calculated using a sampling-based method that estimates empirical variances of true and predicted breeding values from a simulated n-sample. Once the CD matrix was estimated, a clustering method that can handle a large number of comparisons was applied to build compact clusters of connected herds of the Bruna dels Pirineus beef cattle. Since in this breed, natural service is predominant and there are almost no links with reference sires, to estimate CDs, an animal model was used taking into consideration all pedigree information and, especially, the connections with dams. A sensitivity analysis was performed to contrast single-trait sire and animal model evaluations with different heritabilities, multiple-trait animal model evaluations with different degrees of genetic correlations and models with maternal effects. Results: Using a sire model, the percentage of connected herds was very low even for highly heritable traits whereas with an animal model, most of the herds of the breed were well connected and high CD values were obtained among them, especially for highly heritable traits (the mean of average CD per herd was 0.535 for a simulated heritability of 0.40). For the lowly heritable traits, the average CD increased from 0.310 in the single-trait evaluation to 0.319 and 0.354 in the multi-trait evaluation with moderate and high genetic correlations, respectively. In models with maternal effects, the average CD per herd for the direct effects was similar to that from single-trait evaluations. For the maternal effects, the average CD per herd increased if the maternal effects had a high genetic correlation with the direct effects, but the percentage of connected herds for maternal effects was very low, less than 12%. Conclusions: The degree of connectedness in a bovine population bred by natural service mating, such as Bruna del Pirineus beef cattle, measured as the CD of comparisons among herds, is high. It is possible to define a pool of animals for which estimated breeding values can be compared after an across-herds genetic evaluation, especially for highly heritable traits