A comprehensive analysis of the genetic diversity and environmental adaptability in worldwide Merino and Merino-derived sheep breeds

BACKGROUND: To enhance and extend the knowledge about the global historical and phylogenetic relationships between Merino and Merino-derived breeds, 19 populations were genotyped with the OvineSNP50 BeadChip specifically for this study, while an additional 23 populations from the publicly available genotypes were retrieved. Three complementary statistical tests, Rsb (extended haplotype homozygosity between-populations), XP-EHH (cross-population extended haplotype homozygosity), and runs of homozygosity (ROH) islands were applied to identify genomic variants with potential impact on the adaptability of Merino genetic type in two contrasting climate zones. RESULTS: The results indicate that a large part of the Merino's genetic relatedness and admixture patterns are explained by their genetic background and/or geographic origin, followed by local admixture. Multi-dimensional scaling, Neighbor-Net, Admixture, and TREEMIX analyses consistently provided evidence of the role of Australian, Rambouillet and German strains in the extensive gene introgression into the other Merino and Merino-derived breeds. The close relationship between Iberian Merinos and other South-western European breeds is consistent with the Iberian origin of the Merino genetic type, with traces from previous contributions of other Mediterranean stocks. Using Rsb and XP-EHH approaches, signatures of selection were detected spanning four genomic regions located on Ovis aries chromosomes (OAR) 1, 6 and 16, whereas two genomic regions on OAR6, that partially overlapped with the previous ones, were highlighted by ROH islands. Overall, the three approaches identified 106 candidate genes putatively under selection. Among them, genes related to immune response were identified via the gene interaction network. In addition, several candidate genes were found, such as LEKR1, LCORL, GHR, RBPJ, BMPR1B, PPARGC1A, and PRKAA1, related to morphological, growth and reproductive traits, adaptive thermogenesis, and hypoxia responses. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive dataset that includes most of the Merino and Merino-derived sheep breeds raised in different regions of the world. The results provide an in-depth picture of the genetic makeup of the current Merino and Merino-derived breeds, highlighting the possible selection pressures associated with the combined effect of anthropic and environmental factors. The study underlines the importance of Merino genetic types as invaluable resources of possible adaptive diversity in the context of the occurring climate changes

Evaluation of a lithium formate EPR dosimetry system for dose measurements around Ir-192 brachytherapy sources

A dosimetry system using lithium formate monohydrate (HCO2Li center dot H2O) as detector material and electron paramagnetic resonance (EPR) spectroscopy for readout has been used to measure absorbed dose distributions around clinical Ir-192 sources. Cylindrical tablets with diameter of 4.5 mm, height of 4.8 mm, and density of 1.26 g/cm(3) were manufactured. Homogeneity test and calibration of the dosimeters were performed in a 6 MV photon beam. Ir-192 irradiations were performed in a PMMA phantom using two different source models, the GammaMed Plus HDR and the microSelectron PDR-v1 model. Measured absorbed doses to water in the PMMA phantom were converted to the corresponding absorbed doses to water in water phantoms of dimensions used by the treatment planning systems (TPSs) using correction factors explicitly derived for this experiment. Experimentally determined absorbed doses agreed with the absorbed doses to water calculated by the TPS to within +/- 2.9%. Relative standard uncertainties in the experimentally determined absorbed doses were estimated to be within the range of 1.7%-1.3% depending on the radial distance from the source, the type of source (HDR or PDR), and the particular absorbed doses used. This work shows that a lithium formate dosimetry system is well suited for measurements of absorbed dose to water around clinical HDR and PDR Ir-192 sources. Being less energy dependent than the commonly used thermoluminescent lithium fluoride (LiF) dosimeters, lithium formate monohydrate dosimeters are well suited to measure absorbed doses in situations where the energy dependence cannot easily be accounted for such as in multiple-source irradiations to verify treatment plans. Their wide dynamic range and linear dose response over the dose interval of 0.2-1000 Gy make them suitable for measurements on sources of the strengths used in clinical applications. The dosimeter size needs, however, to be reduced for application to single-source dosimetry.Original Publication: Laura Antonovic, Håkan Gustafsson, Gudrun Alm Carlsson and Åsa Carlsson Tedgren, Evaluation of a lithium formate EPR dosimetry system for dose measurements around Ir-192 brachytherapy sources, 2009, MEDICAL PHYSICS, (36), 6, 2236-2247. http://dx.doi.org/10.1118/1.3110068 Copyright: American Institute of Physics http://www.aip.org/</p

A comprehensive analysis of the genetic diversity and environmental adaptability in worldwide Merino and Merino-derived sheep breeds

Background: To enhance and extend the knowledge about the global historical and phylogenetic relationships between Merino and Merino-derived breeds, 19 populations were genotyped with the OvineSNP50 BeadChip specifically for this study, while an additional 23 populations from the publicly available genotypes were retrieved. Three complementary statistical tests, Rsb (extended haplotype homozygosity between-populations), XP-EHH (cross-population extended haplotype homozygosity), and runs of homozygosity (ROH) islands were applied to identify genomic variants with potential impact on the adaptability of Merino genetic type in two contrasting climate zones. Results: The results indicate that a large part of the Merino's genetic relatedness and admixture patterns are explained by their genetic background and/or geographic origin, followed by local admixture. Multi-dimensional scaling, Neighbor-Net, Admixture, and TREEMIX analyses consistently provided evidence of the role of Australian, Rambouillet and German strains in the extensive gene introgression into the other Merino and Merino-derived breeds. The close relationship between Iberian Merinos and other South-western European breeds is consistent with the Iberian origin of the Merino genetic type, with traces from previous contributions of other Mediterranean stocks. Using Rsb and XP-EHH approaches, signatures of selection were detected spanning four genomic regions located on Ovis aries chromosomes (OAR) 1, 6 and 16, whereas two genomic regions on OAR6, that partially overlapped with the previous ones, were highlighted by ROH islands. Overall, the three approaches identified 106 candidate genes putatively under selection. Among them, genes related to immune response were identified via the gene interaction network. In addition, several candidate genes were found, such as LEKR1, LCORL, GHR, RBPJ, BMPR1B, PPARGC1A, and PRKAA1, related to morphological, growth and reproductive traits, adaptive thermogenesis, and hypoxia responses. Conclusions: To the best of our knowledge, this is the first comprehensive dataset that includes most of the Merino and Merino-derived sheep breeds raised in different regions of the world. The results provide an in-depth picture of the genetic makeup of the current Merino and Merino-derived breeds, highlighting the possible selection pressures associated with the combined effect of anthropic and environmental factors. The study underlines the importance of Merino genetic types as invaluable resources of possible adaptive diversity in the context of the occurring climate changes

Catàleg de logotips per a commemorar el 50 aniversari de la fundació d’EINA

Catàleg de logotips dissenyats per a commemorar el 50 aniversari de la fundació d’EINA

Renal Drug Transporters and Drug Interactions.

Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers