Modelos experimentales para el estudio de la patogenia de la muerte embrionaria en tricomonosis bovina y herpesvirosis equina

Desde hace mucho tiempo, por razones prácticas, científicas y éticas, se han desarrollado modelos experimentales con animales de laboratorio para su aplicación en investigaciones biomédicas. Los modelos animales se definen como “organismos vivientes con una inherente adquisición natural a procesos patológicos inducidos o espontáneos que, de una u otra manera, semejan el mismo fenómeno ocurrido en el hospedador natural” (Márquez, 1997). Los animales de laboratorio son modelos muy convenientes y herramientas útiles para utilizar en el estudio de muchas enfermedades infecciosas. En el caso de medicina veterinaria, en especial cuando se trata de enfermedades de grandes animales, el uso del hospedador natural para estudiar aspectos patogénicos e inmunológicos de una infección, muchas veces se torna dificultoso, tanto por las inconveniencias que genera el manejo de estos animales como por el costo que implica. Debido al interés y la complejidad en el estudio de las enfermedades infecciosas, hay una búsqueda en la profundización de los conocimientos del proceso intrínseco de la inmunopatogenia que requiere de la creación de modelos animales alternativos a los hospedadores naturales. El objetivo es generar diseños experimentales confiables y reproducibles, desarrollables en medios controlados en espacios reducidos y con menor costo. Entre las múltiples ventajas que derivan de la utilización de modelos experimentales en el estudio de diferentes enfermedades, se mencionan las siguientes como las más importantes: • Conocer la historia natural de la enfermedad, cuya etiología, patogenia, sintomatología y evolución pueden mantenerse en condiciones experimentales, sin la influencia de factores extraños que la modifiquen. • Reproducir la enfermedad en forma experimental, casi a voluntad, lo que permite disponer de la casuística necesaria. • Realizar estudios fisiopatológicos, desarrollando nuevas técnicas diagnósticas para tal enfermedad. • Estudiar las enfermedades en animales endocriados lo que permite un amplio campo de investigación en inmunología, patología y genética, entre otras áreas (Cuba Caparó, 1982). En la selección de la especie utilizada como modelo animal es importante tener en cuenta algunas características generales: a) que permita la transferencia de la información, b) bajo costo y disponibilidad permanentes, c) generalización de los resultados, d) facilidad y adaptabilidad a la manipulación experimental, e) que se pueda contar con un número de animales necesarios para realizar el experimento, f) tiempo de vida, edad en que se alcanza la adultez y generación del número de progenies necesarias en poco tiempo, g) consecuencias ecológicas e implicancias éticas de su uso (Klein, 2000).Incluye las palabras de presentación del proyecto a cargo del Dr. Carlos O. Scoppa.Academia Nacional de Agronomía y Veterinari

Avianbase: a community resource for bird genomics

Giving access to sequence and annotation data for genome assemblies is important because, while facilitating research, it places both assembly and annotation quality under scrutiny, resulting in improvements to both. Therefore we announce Avianbase, a resource for bird genomics, which provides access to data released by the Avian Phylogenomics Consortium

Third Report on Chicken Genes and Chromosomes 2015

Following on from the First Report on Chicken Genes and Chromosomes [Schmid et al., 2000] and the Second Report in 2005 [Schmid et al., 2005], we are pleased to publish this long-awaited Third Report on the latest developments in chicken genomics. The First Report highlighted the availability of genetic and physical maps, while the Second Report was published as the chicken genome sequence was released. This report comes at a time of huge technological advances (particularly in sequencing methodologies) which have allowed us to examine the chicken genome in detail not possible until now. This has also heralded an explosion in avian genomics, with the current availability of more than 48 bird genomes [Zhang G et al., 2014b; Eöry et al., 2015], with many more planned

Contributions of protein-coding and regulatory change to adaptive molecular evolution in murid rodents

The contribution of regulatory versus protein change to adaptive evolution has long been controversial. In principle, the rate and strength of adaptation within functional genetic elements can be quantified on the basis of an excess of nucleotide substitutions between species compared to the neutral expectation or from effects of recent substitutions on nucleotide diversity at linked sites. Here, we infer the nature of selective forces acting in proteins, their UTRs and conserved noncoding elements (CNEs) using genome-wide patterns of diversity in wild house mice and divergence to related species. By applying an extension of the McDonald-Kreitman test, we infer that adaptive substitutions are widespread in protein-coding genes, UTRs and CNEs, and we estimate that there are at least four times as many adaptive substitutions in CNEs and UTRs as in proteins. We observe pronounced reductions in mean diversity around nonsynonymous sites (whether or not they have experienced a recent substitution). This can be explained by selection on multiple, linked CNEs and exons. We also observe substantial dips in mean diversity (after controlling for divergence) around protein-coding exons and CNEs, which can also be explained by the combined effects of many linked exons and CNEs. A model of background selection (BGS) can adequately explain the reduction in mean diversity observed around CNEs. However, BGS fails to explain the wide reductions in mean diversity surrounding exons (encompassing ~100 Kb, on average), implying that there is a substantial role for adaptation within exons or closely linked sites. The wide dips in diversity around exons, which are hard to explain by BGS, suggest that the fitness effects of adaptive amino acid substitutions could be substantially larger than substitutions in CNEs. We conclude that although there appear to be many more adaptive noncoding changes, substitutions in proteins may dominate phenotypic evolution

Inference of Mutation Parameters and Selective Constraint in Mammalian Coding Sequences by Approximate Bayesian Computation

We develop an inference method that uses approximate Bayesian computation (ABC) to simultaneously estimate mutational parameters and selective constraint on the basis of nucleotide divergence for protein-coding genes between pairs of species. Our simulations explicitly model CpG hypermutability and transition vs. transversion mutational biases along with negative and positive selection operating on synonymous and nonsynonymous sites. We evaluate the method by simulations in which true mean parameter values are known and show that it produces reasonably unbiased parameter estimates as long as sequences are not too short and sequence divergence is not too low. We show that the use of quadratic regression within ABC offers an improvement over linear regression, but that weighted regression has little impact on the efficiency of the procedure. We apply the method to estimate mutational and selective constraint parameters in data sets of protein-coding genes extracted from the genome sequences of primates, murids, and carnivores. Estimates of CpG hypermutability are substantially higher in primates than murids and carnivores. Nonsynonymous site selective constraint is substantially higher in murids and carnivores than primates, and autosomal nonsynonymous constraint is higher than X-chromsome constraint in all taxa. We detect significant selective constraint at synonymous sites in primates, carnivores, and murid rodents. Synonymous site selective constraint is weakest in murids, a surprising result, considering that murid effective population sizes are likely to be considerably higher than the other two taxa

Effects of different anesthetics in the murine model of EHV-1 infection

Mice are commonly used as an experimental model to investigate the Equid herpesvirus 1 (EHV-1) infection. This model easily reproduces the disease, and the clinical signs are more or less similar to those observed in the horse, the natural host. During natural infection, the acute course of respiratory infection is mandatory for the development of adaptive immune response. Since interactions between EHV-1 and anesthetics are possible, the study investigated whether the early events of murine pulmonary immune response could be affected by different anesthetics. Therefore, mice were experimentally infected with a unique EHV-1 strain under the effects of ether, ketamine/xylazine, or isoflurane. Clinical signs and histopathological lesions in the lungs were described, and the cell death and proliferation rates of sham-inoculated or infected animals were quantified using immunohistochemistry. Clinical signs were more severe in animals anesthetized with ether. Qualitative differences in the recruited inflammatory cells were observed following application of anesthesia. The level of infection between the infected groups was not statistically significant. However, lungs from ketamine/xylazine-anesthetized animals showed the highest cell death rates, whereas those from isoflurane-anesthetized animals showed the highest proliferation rates. It has been emphasized that anesthetics alone or their interactions with EHV-1 modify the response against the infection. An appropriate selection of the anesthetic during experimental studies is relevant to minimize wrong conclusions.Fil: Eöry, M. L.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Zanuzzi, Carolina Natalia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fuentealba, Nadia Analia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sguazza, Guillermo Hernán. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Gimeno, Eduardo Juan. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galosi, Cecilia Monica. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Estimates of mean nucleotide diversity (<i>π</i>) in house mice, divergence to rat (<i>d_rat</i>) and their ratio (<i>π</i>/<i>d</i>) plotted against the distance from the nearest protein-coding exon (panel A) or CNE (panel B).

<p>Mean estimates of <i>π</i>/<i>d</i> can be approximated well by a negative exponential function (red line), obtained by fitting the function f(<i>x</i>) = <i>A</i>(1-<i>B</i>(exp(-<i>x/d</i>))) to mean <i>π</i>/<i>d</i> by nonlinear least squares (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003995#s4" target="_blank">Materials and Methods</a> for details). The bottom panel shows the number of sites (in Mb) on a log scale that contribute to each bin.</p

Results from DFE-alpha.

<p><i>n_t</i> is the total number of sites in the reference genome corresponding to each mutually exclusive site class (including non-canonical spliceforms in the case of protein-coding exons). <i>N_es</i> (the product of the mean homozygous effect of a deleterious mutation and the effective population size) and <i>β</i> (the gamma shape parameter, which has a lower estimable value of 0.05 within DFE-alpha) are the inferred parameters of the DFE, from which we calculate the mean fixation probability of a deleterious mutation relative to a neutral mutation (<i>u_n</i>) and estimates of the proportion of deleterious mutations in three ranges of fitness effects (on a scale of <i>N_es</i> = 0–1, 1–10 and 10+). From estimates of divergence from rat at selected and neutral sites, we calculate estimates of the proportion of adaptive substitutions (<i>α</i>) and the rate of adaptive substitution relative to the rate of synonymous substitution (<i>ω_a</i>) (results are shown for non-CpG-prone sites). <i>n_a</i> is an estimate of the total number of adaptive substitutions between mouse and rat attributable to each site class and is calculated from <i>n_a</i> = <i>ω_a n_t d_s</i>, where <i>d_s</i> = 0.18, an estimate of divergence for synonymous sites. 95% confidence limits are shown in square brackets.</p

Patterns of nucleotide diversity (<i>π</i>), divergence to rat (<i>d</i>) and <i>π/d</i>, in the flanks of zero-fold degenerate and four-fold degenerate protein-coding sites identified as either having a fixed substitution between <i>M. m. castaneus</i> and <i>M. famulus</i> or no substitution.

<p>Patterns of nucleotide diversity (<i>π</i>), divergence to rat (<i>d</i>) and <i>π/d</i>, in the flanks of zero-fold degenerate and four-fold degenerate protein-coding sites identified as either having a fixed substitution between <i>M. m. castaneus</i> and <i>M. famulus</i> or no substitution.</p