Deletion in the EVC2 gene causes chondrodysplastic dwarfism in Tyrolean Grey cattle.

During the summer of 2013 seven Italian Tyrolean Grey calves were born with abnormally short limbs. Detailed clinical and pathological examination revealed similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common founder, assuming autosomal monogenic recessive transmission of the defective allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was associated with the disease. Whole genome re-sequencing of an affected calf revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature stop codon in the coding sequence of bovine EVC2, and was concordant with the recessive pattern of inheritance in affected and carrier animals. This loss of function mutation confirms the important role of EVC2 in bone development. Genetic testing can now be used to eliminate this form of chondrodysplastic dwarfism from Tyrolean Grey cattle.

Prevalence of paunch calf syndrome carriers in Italian Romagnola cattle.

The term 'paunch calf syndrome' encompasses the multi-organic lethal developmental dysplasia reported in the Romagnola breed of cattle and is characterised by facial deformities, an enlarged and floating abdomen containing considerable abdominal effusion, and hepatic fibrosis. Paunch calf syndrome is caused by a missense mutation in the KDM2B gene (c.2503G>A) that is thought to lead to an amino acid exchange (p.D835N). In this study, the prevalence of carriers of the mutant KDM2B allele (and thus the frequency of the allele) was assessed in selected subpopulations of Romagnola cattle. The prevalence of carriers within top-ranked Romagnola sires over the years 2007-2012 was 29.3% (allele frequency 14.6%). In young bull calves, 30.9% were carriers with an allele frequency of 15.4%.

Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle

Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.

Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: an animal model of human Brody disease

Congenital pseudomyotonia in Chianina cattle is a muscle function disorder very similar to that of Brody disease in humans. Mutations in the human ATP2A1 gene, encoding SERCA1, cause Brody myopathy. The analysis of the collected Chianina pedigree data suggested monogenic autosomal recessive inheritance and revealed that all 17 affected individuals traced back to a single founder. A deficiency of SERCA1 function in skeletal muscle of pseudomyotonia affected Chianina cattle was observed as SERCA1 activity in affected animals was decreased by about 70%. Linkage analysis showed that the mutation was located in the ATP2A1 gene region on BTA25 and subsequent mutation analysis of the ATP2A1 exons revealed a perfectly associated missense mutation in exon 6 (c.491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease.

Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization

Ellis-van Creveld (EvC) syndrome is a human autosomal recessive disorder caused by a mutation in either the EVC or EVC2 gene, and presents with short limbs, polydactyly, and ectodermal and heart defects. The aim of this study was to understand the pathologic basis by which deletions in the EVC2 gene lead to chondrodysplastic dwarfism and to describe the morphologic, immunohistochemical, and molecular hallmarks of EvC syndrome in cattle. Five Grey Alpine calves, with a known mutation in the EVC2 gene, were autopsied. Immunohistochemistry was performed on bone using antibodies to collagen II, collagen X, sonic hedgehog, fibroblast growth factor 2, and Ki67. Reverse transcription polymerase chain reaction was performed to analyze EVC1 and EVC2 gene expression. Autopsy revealed long bones that were severely reduced in length, as well as genital and heart defects. Collagen II was detected in control calves in the resting, proliferative, and hypertrophic zones and in the primary and secondary spongiosa, with a loss of labeling in the resting zone of 2 dwarfs. Collagen X was expressed in hypertrophic zone in the controls but was absent in the EvC cases. In affected calves and controls, sonic hedgehog labeled hypertrophic chondrocytes and primary and secondary spongiosa similarly. FGF2 was expressed in chondrocytes of all growth plate zones in the control calves but was lost in most EvC cases. The Ki67 index was lower in cases compared with controls. EVC and EVC2 transcripts were detected. Our data suggest that EvC syndrome of Grey Alpine cattle is a disorder of chondrocyte differentiation, with accelerated differentiation and premature hypertrophy of chondrocytes, and could be a spontaneous model for the equivalent human disease.

Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation

Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal species, we identified TSR2 as a regulator of hair follicle development.

Besnoitia besnoiti lytic cycle in vitro and differences in invasion and intracellular proliferation among isolates

Background Bovine besnoitiosis, caused by the protozoan Besnoitia besnoiti, reduces productivity and fertility of affected herds. Besnoitiosis continues to expand in Europe and no effective control tools are currently available. Experimental models are urgently needed. Herein, we describe for the first time the kinetics of standardised in vitro models for the B. besnoiti lytic cycle. This will aid to study the pathogenesis of the disease, in the screening for vaccine targets and drugs potentially useful for the treatment of besnoitiosis. Methods We compared invasion and proliferation of one B. tarandi (from Finland) and seven B. besnoiti isolates (Bb-Spain1, Bb-Spain2, Bb-Israel, Bb-Evora03, Bb-Ger1, Bb-France, Bb-Italy2) in MARC-145 cell culture. Host cell invasion was studied at 4, 6, 8 and 24 h post infection (hpi), and proliferation characteristics were compared at 24, 48, 72, 96, 120, and 144 hpi. Results In Besnoitia spp., the key parameters that determine the sequential adhesion-invasion, proliferation and egress steps are clearly distinct from those in the related apicomplexans Toxoplasma gondii and Neospora caninum. Besnoitia spp. host cell invasion is a rather slow process, since only 50 % of parasites were found intracellular after 3–6 h of exposure to host cells, and invasion still took place after 24 h. Invasion efficacy was significantly higher for Bb-France, Bb-Evora03 and Bb-Israel. In addition, the time span for endodyogeny to take place was as long as 18–35 h. Bb-Israel and B. tarandi isolates were most prolific, as determined by the tachyzoite yield at 72 hpi. The total tachyzoite yield could not be predicted neither by invasion-related parameters (velocity and half time invasion) nor by proliferation parameters (lag phase and doubling time (dT)). The lytic cycle of Besnoitia was asynchronous as evidenced by the presence of three different plaque-forming tachyzoite categories (lysis plaques, large and small parasitophorous vacuoles). Conclusions This study provides first insights into the lytic cycle of B. besnoiti isolates and a standardised in vitro model that allows screening of drug candidates for the treatment of besnoitiosis.

Producción de bolsas con válvula tipo Bag in Box para la industria vitivinícola

El presente estudio de prefactibilidad detalla el tipo particular de envase Bag in Box en la industria vitivinícola y analiza las múltiples ventajas para los sectores en los cuales puede ser aplicado. Teniendo en cuenta que en Argentina el consumo de vino en Bag in Box ha crecido de manera exponencial en los últimos años, se ha analizado el mercado consumidor de vino en dichos envases ya que no existe información estadística completa respecto a su consumo como tal.

Producción de barniz de base alquídica

El presente trabajo contiene el análisis y la evaluación técnico económica de la fabricación de barniz a nivel industrial. El estudio realizado alcanza el nivel de prefactibilidad. El producto barniz es de tipo bien intermedio, utilizado en un importante número de aplicaciones, mayormente para los recubrimientos en la industria automotriz y de la construcción. El tamaño propuesto para la planta fue determinado a partir del análisis y consideración de las siguientes variables: tecnologías aplicables, disponibilidad de insumos, mercado potencial a sustituir, tasa de descuento de referencia y requerimientos de gestión

Producción de confituras con integración socio laboral

El presente proyecto de inversión plantea la elaboración de productos alimenticios, orientado a la producción de confituras y sus derivados, con la posibilidad de desarrollar nuevos productos a partir de la materia prima local, permitiendo desarrollar un modelo de industria de complementariedad socio laboral. Se desarrolla el análisis de la viabilidad técnica y económica de una planta elaboradora de mermeladas, dulces y jaleas. El análisis permitirá determinar los recursos necesarios para su puesta en marcha y su rentabilidad.

El neutralismo ontológico de Rudolf Carnap

Fil: Gaeta, Rodolfo Luján. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Del Derecho del Niño al derecho a ser niño. La concepción de la infancia en una institución para 'chicos de la calle'

El Centro de Atención Integral a Niños y Adolescentes (CAINA-GCBA) se propone trabajar con los niños, niñas y adolescentes que se encuentran en situación de calle y que se acercan voluntariamente a la institución, desde la perspectiva de los Derechos del Niño. Más allá de las definiciones formales acerca de los destinatarios (de 8 a 18 años), es en las interacciones cotidianas entre las personas que allí trabajan y las que se acercan donde se ponen en juego de manera práctica los criterios para definir quiénes son los ?chicos? que accederán a los recursos para la asistencia (y quiénes no), y cuál será el sentido de esa intervención. En este trabajo nos interesa recrear, a través del análisis de entrevistas al personal y de la observación participante de las interacciones entre éstos y los "chicos" que asisten, la manera en que desde esta institución se concibe el estatus social del "ser niño" (y sus características), y como consecuencia, se propone intervenir en una población en la que los atributos de esa infancia no aparecen como dados y evidentes

Les chaînes de références dans des corpus textuels trilingues : Critères et finalité de la recherche

En la obra Stylistique comparée du français et de l?anglais, Vinay y Darbelnet señalan el valor de la traducción como disciplina auxiliar de la Lingüística (1977: 25). Sin entrar en el debate sobre el alcance de las nociones de traducción y transcodificación, se entiende que en toda situación de lenguas en contactos, como es el caso de la traducción, el universal de interferencia influye sobre los mecanismos discursivos relacionados con la memoria, de manera tal que la producción de un texto traducido sin visibilidad de interferencia supone esfuerzos especiales por parte del traductor (Toury, 2004: 345). En el marco de esta problemática, nuestro estudio respecto de las cadenas referenciales (CR) en corpora trilingües se fundamenta en los trabajos de Ariel (1990) y, especialmente de Schnedecker (1997, 2005), en cuanto a las expresiones referenciales que mantienen la cohesión del texto y sus relaciones con la accesibilidad al referente. Los resultados de este estudio descriptivo y contrastivo a partir de un corpus de textos trilingües podrán contribuir al conocimiento del macroproceso de traducción y, por consiguiente, a la formación de traductores. Asimismo, esta presentación se inscribe en el marco de la Traductología y aspira a ser un aporte a otras disciplinas, especialmente a la Lingüística, en una relación de reciprocidad (García, 2012: 78)

De la Argentina al mundo hispanoamericano : Las traducciones con acento porteño de la obra de Simone de Beauvoir

Fil: Cagnolati, Beatriz. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.