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Abstract A first generation clone-based physical map for the bovine genome was constructed combining, fluorescent double digestion fingerprinting and sequence tagged site (STS) marker screening. The BAC clones were selected from an Inra BAC library (105 984 clones) and a part of the CHORI-240 BAC library (26 500 clones). The contigs were anchored using the screening information for a total of 1303 markers (451 microsatellites, 471 genes, 127 EST, and 254 BAC ends). The final map, which consists of 6615 contigs assembled from 100 923 clones, will be a valuable tool for genomic research in ruminants, including targeted marker production, positional cloning or targeted sequencing of regions of specific interest.

Se estudió la presencia de los anticuerpos anti-AgsHB en 1 280 niños con edades entre 7 meses y 3 años, que recibieron la vacuna cubana antihepatitis B, Heberbiovac-HB al nacimiento, al mes y 6 meses de edad dentro del Programa Nacional de Inmunización en Cuba. Se determinó la presencia del AgsHB y se cuantificaron los anticuerpos en el suero mediante métodos ELISA sandwich, desarrollados y validados en el Laboratorio de Inmunología. Teniendo en cuenta el tiempo transcurrido desde el final de la vacunación, la muestra se dividió en 3 grupos: entre 7 meses y 1 año, entre 1 y 2 años, y entre 2 y 3 años. Ninguno de los niños presentó marcadores de infección y los porcentajes de seroprotección fueron 96,6 en el grupo de 7 meses a 1 año, y de 100 en los grupos de 1 a 2 y de 2 a 3 años. Los porcentajes de niños con cifras de anti-AgsHB superiores o iguales a 100 UI/L fueron de 93,1, 90,7 y 77,8, respectivamente. Las medias geométricas de anti-AgsHB fueron de 1 056, 699 y 483 UI/L para cada grupo. Se encontraron diferencias significativas en los porcentajes de seroprotección, hiperrespuesta y medias geométricas de anti-AgsHB cuando se compararon estas variables entre niños con historia de asma bronquial (687,8, 620,2, y 402,9 UI/L) y otros sin este antecedente en los 3 grupos (1 341, 1 047,8, y 528,3 UI/L); las concentraciones fueron mucho más elevadas en los no asmáticos. Estos resultados podrían indicar que aún con antígenos no alergénicos se puede inducir una respuesta a predominio Th 2 en asmáticos y que por causa de la citofilia de las inmunoglobulinas de clase E los anticuerpos no son detectados, o bien que la respuesta es de hecho menor como consecuencia del carácter de disreactor de los asmáticos. Se concluye que la inmunogenicidad de la vacuna en una población abierta es comparable a la de los estudios controlados, y que no se necesita dosis de refuerzo al menos después de transcurridos 4 años de finalizado el esquema, si se tiene en cuenta la cinética de desaparición del anti-AgsHB. Se requiere un estudio controlado en poblaciones de asmáticos, que permita verificar los resultados obtenidos y darles explicaciónThe presence of anti-AgsHB antibodies was studied in 1 280 children aged from 7 months to 3 years, who were administered the Cuban anti-hepatitis B vaccine Heberbiovac HB when they were born, at 1 and 6 months of age as part of the National Immunization Program in Cuba. AgsHB was detected and serum antibodies were determined by ELISA sandwich methods, developed and validated in the Immunology Laboratory. Considering the time elapsed from the end of the vaccination, the sample was divided into 3 groups: 7 months to 1 year, 1-2 years, and 2-3 years of age. None of the children exhibited infection markers and seroprotection percentages were 96.6 in 7months to 1 year old group, and 100% in 1-2 years-old and 2-3 years-old groups. The percentages of children with anti-HbsAg values equal to or over 100 UI/L were 93.1%, 90.7% and 77.8% respectively. The geometric means of anti-HbsAg were 1 0567, 699 and 483 UI/L respectively. Significant differences were found in seroprotection and hyperesponse percentages and in anti-HbsAg geometric means when comparing these variables between children with bronchial asthma history (687.8, 620.2 and 402.9 UI/L) and non-asthmatic children of the 3 groups(1 341, 1 047.8 and 528.3 UI/L); the concentrations were much higher in non-asthmatics. These outcomes could signal that even with non-allergenic antigens, a predominant Th2 response may be induced in asthmatic children and that wither antibodies are not detected due to IgE cytophilia or response is in fact lower as a result of the disreactor nature of the asthmatics. It is concluded that immunogenicity of the vaccine in a population is comparable to that of the controlled studies and that a reinforcement dose is not needed at least 4 years after the completion of the immunization schedule if one takes into account the kinetics of anti-HbsAg elimination. A controlled study of asthmatic populations is required to verify the achieved results with due explanations

Abstract Advances in imaging and biological targeting have led to the development of stereotactic body radiation therapy (SBRT) as an alternative treatment of extracranial oligometastases. New radiobiological concepts, such as ceramide-induced endothelial apoptosis after hypofractionated high-dose SBRT, and the identification of patients with oligometastatic disease by microRNA expression may yet lead to further developments. Key factors in SBRT are delivery of a high dose per fraction, proper patient positioning, target localisation, and management of breathing–related motion. Our review addresses the radiation doses and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland oligometastases and treatment outcomes. Reported local control (LC) rates for liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 -100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are rare. SBRT of adrenal gland oligometastases shows promising results in the case of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe and effective treatment option for abdominal oligometastases.

Abstract Background Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies. Results EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC. Conclusion This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions.

Abstract Background Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6× coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. Results An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6× bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. Conclusion Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6× sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.

Abstract Background Comparative mapping provides new insights into the evolutionary history of genomes. In particular, recent studies in mammals have suggested a role for segmental duplication in genome evolution. In some species such as Drosophila or maize, transposable elements (TEs) have been shown to be involved in chromosomal rearrangements. In this work, we have explored the presence of interspersed repeats in regions of chromosomal rearrangements, using an updated high-resolution integrated comparative map among cattle, man and mouse. Results The bovine, human and mouse comparative autosomal map has been constructed using data from bovine genetic and physical maps and from FISH-mapping studies. We confirm most previous results but also reveal some discrepancies. A total of 211 conserved segments have been identified between cattle and man, of which 33 are new segments and 72 correspond to extended, previously known segments. The resulting map covers 91% and 90% of the human and bovine genomes, respectively. Analysis of breakpoint regions revealed a high density of species-specific interspersed repeats in the human and mouse genomes. Conclusion Analysis of the breakpoint regions has revealed specific repeat density patterns, suggesting that TEs may have played a significant role in chromosome evolution and genome plasticity. However, we cannot rule out that repeats and breakpoints accumulate independently in the few same regions where modifications are better tolerated. Likewise, we cannot ascertain whether increased TE density is the cause or the consequence of chromosome rearrangements. Nevertheless, the identification of high density repeat clusters combined with a well-documented repeat phylogeny should highlight probable breakpoints, and permit their precise dating. Combining new statistical models taking the present information into account should help reconstruct ancestral karyotypes.