Marco V. José

Limitations of current diagnostic procedures for the diagnosis of Taenia solium cysticercosis in rural pigs

The aim of the present study was to evaluate diagnostic procedures for porcine cysticercosis. Sera were obtained from 32 pigs reared in commercial farms, 47 pigs before and after experimental infection, 42 carefully necropsied rural pigs and 191 slaughtered pigs from rural communities in which the presence of the Taenia solium metacestode was assessed by tongue dissection. Sera were analyzed by ELISA to detect antibodies against T. solium antigens and to detect parasite antigens. Most sera from the necropsied rural pigs were also evaluated by the Western blot method. Antigen and antibody ELISA detection assays showed high sensitivity and specificity when applied to sera from pigs reared in commercial farms. In contrast, all methods (Ag-ELISA, Ab-ELISA assays, EITB and tongue inspection) showed lower sensitivity and specificity when applied to the generally lightly infected rurally reared pigs. The probability distribution of cysts in carcasses were also determined. These results emphasize the difficulties in detecting cysticercosis in rural pigs with low levels of cyst burdens.

INHIBITORY ROLE OF ANTIBODIES IN THE DEVELOPMENT OF TAENIA SOLIUM AND TAENIA CRASSICEPS TOWARD REPRODUCTIVE AND PATHOGENIC STAGES

Untreated Taenia solium cysticerci obtained from different naturally infected pigs vary notably in their capacity to develop into intestinal tapeworms in prednisolone-treated hamsters, whereas cells derived from Taenia crassiceps cysticerci after 2 mo of infection almost always develop to cysticerci in the peritoneal cavity of susceptible BALB/cAnN mice. Preincubation of whole cysticerci or parasite cells with mice immunoglobulins raised against an 18-mer peptide epitope (GK-1) common to both parasites significantly interferes with both transformations. These crippling effects of antiparasite antibodies suggest new forms of immunological interference with parasite biology other than simple killing. Antibodies that cripple biological functions of the parasite, e.g., their development to reproductive or pathogenic stages, make them important protagonists in taeniasis/cysticercosis disease as classic parasitocidal antibodies. Different serum levels of crippling antibodies in the infected pigs could be responsible for the varied ability of cysticerci to convert to tapeworms. Antigens capable of inducing crippling antibodies, e.g., GK-1, could be useful as a therapeutic vaccine for pigs in order to reduce parasite transmission.

Vaccination against Taenia solium cysticercosis in underfed rustic pigs of México: roles of age, genetic background and antibody response.

Vaccination of pigs of mixed genetic make-up, raised as rustically as done in rural Mexico, resulted in effective protection to experimental challenge against Taenia solium cysticercosis. Maximum protection was achieved if pigs were immunized at 70 days of age. There was large variation of viable parasite load within vaccinated pigs and controls, which is suggestive of significant genetic factors influencing susceptibility, besides immunization. Our results strengthen the advisability of pig vaccination for control of T. solium cysticercosis, since it lowers the number of viable cysticerci capable of transforming into tapeworms.

Human Tumor Growth Is Inhibited by a Vaccinia Virus Carrying the E2 Gene of Bovine Papillomavirus

Papillomavirus is the etiologic agent associated with cervical carcinoma. The papilloma E2 protein is able to regulate negatively the expression of E6 and E7 papilloma oncoproteins. Therefore, a new, highly attenuated vaccinia virus known as modified vaccinia virus Ankara (MVA), which carries the papillomavirus E2 gene, was used for the treatment of tumors associated with human papillomavirus.

On the evolution of the standard genetic code: vestiges of critical scale invariance from the RNA world in current prokaryote genomes.

Herein two genetic codes from which the primeval RNA code could have originated the standard genetic code (SGC) are derived. One of them, called extended RNA code type I, consists of all codons of the type RNY (purine-any base-pyrimidine) plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. In order to test if putative nucleotide sequences in the RNA World and in both extended RNA codes, share the same scaling and statistical properties to those encountered in current prokaryotes, we used the genomes of four Eubacteria and three Archaeas. For each prokaryote, we obtained their respective genomes obeying the RNA code or the extended RNA codes types I and II. In each case, we estimated the scaling properties of triplet sequences via a renormalization group approach, and we calculated the frequency distributions of distances for each codon. Remarkably, the scaling properties of the distance series of some codons from the RNA code and most codons from both extended RNA codes turned out to be identical or very close to the scaling properties of codons of the SGC. To test for the robustness of these results, we show, via computer simulation experiments, that random mutations of current genomes, at the rates of 10−10 per site per year during three billions of years, were not enough for destroying the observed patterns. Therefore, we conclude that most current prokaryotes may still contain relics of the primeval RNA World and that both extended RNA codes may well represent two plausible evolutionary paths between the RNA code and the current SGC.

Origin and evolution of the Peptidyl Transferase Center from proto‐tRNAs

We tested the hypothesis of Tamura (2011) [3] that molecules of tRNA gave origin to ribosomes, particularly to the Peptidyl Transferase Center (PTC) of the 23S ribosomal RNA. We reconstructed the ancestral sequences from all types of tRNA and compared them in their sequences with the current PTC of 23S ribosomal RNA from different organisms. We built an ancestral sequence of proto‐tRNAs that showed a remarkable overall identity of 50.53% with the catalytic site of PTC. We conclude that the Peptidyl Transferase Center was indeed originated by the fusion of ancestral sequences of proto‐tRNA.

Alternative interpretation of unusual scatchard plots contribution of interactions and heterogeneity

Abstract Simulated binding reactions based on the stoichiometric binding model of Klotz [11] indicate that positive and negative site-site interactions in homogeneous and heterogeneous macromolecules result in varied binding isotherms, some with quite unusual shapes. Our findings provide the basis for some alternative interpretations of binding isotherms, distinct from those commonly found in the current literature.

Evolution of transfer RNA and the origin of the translation system.

The origin of the translation system is at the center of discussions about the evolution of biological systems. In this context, molecules of transfer RNA (tRNA) are highlighted due to its ability to convey the information contained in nucleic acids with the functional information contained in the proteins. Despite many characteristics shared among tRNAs in various organisms, suggesting a monophyletic origin for this group of molecules, recent discussions have proposed a polyphyletic origin for this group, thus indicating that the shared features are products of evolutionary convergence (Di Giulio, 2013). The main arguments in favor of the model for polyphyletic origin of tRNAs, is based on the theory of exons and suggests that the introns played an important role uniting mini exons or genes, which enabled that minigenes with independent origins were grouped in a single transcription unit at the start of the biological system (Di Giulio, 2012a). Genes for tRNAs have one of the most conserved introns that we know, which would represent a remnant of the process that gave rise to this molecule, being the anticodon loop initially a minigene that was attached to the other loop or hairpin that gave origin to the modern structure of tRNAs (Di Giulio, 2012b). An evidence of this model was found in Nanoarchaeum equitans, where a single tRNA is encoded by two genes that are united after the transcription (Randau et al., 2005). Podar et al. (2013), analyzed the genome of N. equitans and suggested that the organization of genes in this organism is a derived character, being consequence of a process of genomic reduction that is associated with their lifestyle (Podar et al., 2013). Thus, the tRNAs would be monophyletic, having a single ancestor that gave origin to the diversity known today, as suggested by Lacey and Staves (1990).

Analysis of bilateral inverse symmetry in whole bacterial chromosomes.

The positions of the 64 DNA tri-nucleotides (triplets) along the Borrelia burgdorferi chromosome were determined and cumulative position plots (CPP) were obtained. Analysis of CPP for complementary triplets revealed close correlations in complementary triplet frequencies (CTF) between opposing leading and lagging strands. Such bilateral inverse symmetry (BIS) applied also to complementary mono- and di-nucleotides and to some >3 n-tuples. At the level of individual bases BIS explains Chargaffs second parity rule for whole bacterial chromosomes. Using shuffled control sequences we show that single-base BIS was not the source of higher-order BIS. Analysis of CTF in 45 other chromosomes suggests that BIS is a general property of eubacteria. BIS at the various levels may be due to the very similar numbers of codons used in chromosomal halves. Evolutionarily, BIS could have resulted from asymmetric substitution of bases combined with genetic rearrangements. However, the provocative theoretical alternative of whole-genome inverse duplication is here considered.

Epidemiological model of diarrhoeal diseases and its application in prevention and control

In this paper, a prototype epidemiological model of acute bacterial and viral diarrhoeal diseases occurring in young children is formulated. The model is able to mimic the observed epidemiological patterns of infantile diarrhoeal diseases associated mainly with enterotoxigenic Escherichia coli or with rotavirus. The proposed mathematical model predicts a plausible pattern of the serological profile of an enteric infection. According to computer simulation experiments (CSE) with this model, it is not necessary to develop an enteric vaccine conferring total and long-lasting immunity in order to achieve protection from diarrhoeal diseases in young children. Given a protective efficacy and a finite duration of vaccine-induced protection, the optimal immunization policy must be sought. Oral rehydration therapy (ORT) intervention has a clear effect in diminishing the number of individuals dying from diarrhoeal illness. The CSE also predict an apparent reduction in age-prevalence of diarrhoeal diseases by use of ORT.