Assessing the spatial dependence of adaptive loci in 43 European and Western Asian goat breeds using AFLP markers

Background During the past decades, neutral DNA markers have been extensively employed to study demography, population genetics and structure in livestock, but less interest has been devoted to the evaluation of livestock adaptive potential through the identification of genomic regions likely to be under natural selection. Methodology/Principal findings Landscape genomics can greatly benefit the entire livestock system through the identification of genotypes better adapted to specific or extreme environmental conditions, therefore we analyzed 101 AFLP markers in 43 European and Western Asian goat breeds both with the software MATSAM, based on a correlative approach (SAM), and with MCHEZA and BAYESCAN, two FST based software able to detect markers carrying signatures of natural selection. MATSAM identified four loci possibly under natural selection - also confirmed by FSToutlier methods - and significantly associated with environmental variables such as diurnal temperature range, frequency of precipitation, relative humidity and solar radiation. Conclusions/Significance These results show that landscape genomics can provide useful information on the environmental factors affecting the adaptive potential of livestock living in specific climatic conditions. Besides adding conservation value to livestock genetic resources, this knowledge may lead to the development of novel molecular tools useful to preserve the adaptive potential of local breeds during genetic improvement programs, and to increase the adaptability of industrial breeds to changing environments

TRACEABILITY OF FOUR EUROPEAN PROTECTED GEOGRAPHIC INDICATION (PGI) BEEF PRODUCTS USING SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) AND BAYESIAN STATISTICS

The use of SNPs in combination with Bayesian statistics for the geographic traceability of cattle were evaluated using a dataset comprising 24 breeds from Italy,France,Spain, Denmark, the Netherlands,Switzerland and UK genotyped with 90 polymorphic markers. The percentage of correct assignment of the individuals to their Country of origin was 90%, with an average assignment probability of 93% and an average specificity of 92%. The higher value was observed for UK breeds (97% of correct assignment) while Swiss animals were the most difficult to allocate (77% of correct assignment). Tracing of Protected Geographic Indication (PGI) products, the approach correctly assigned 100% of Guaranteed Pure Highland Beef; 97% of “Vitellone dell’Appennino Centrale” breeds; 84% of Ternera de Navarra, and 80% of Boeuf de Chalosse. Methods to verify Products of Designated Origin (PDO) and Protected Geographic Indication (PGI) products will help to protect regional foods and promote the economic growth of marginal rural areas by encouraging the product on of high quality niche market foods

Genetic diversity of Italian goat breeds assessed with a medium-density SNP chip

Background: Among the European countries, Italy counts the largest number of local goat breeds. Thanks to the recent availability of a medium-density SNP (single nucleotide polymorphism) chip for goat, the genetic diversity of Italian goat populations was characterized by genotyping samples from 14 Italian goat breeds that originate from different geographical areas with more than 50 000 SNPs evenly distributed on the genome. Results: Analysis of the genotyping data revealed high levels of genetic polymorphism and an underlying North-south geographic pattern of genetic diversity that was highlighted by both the first dimension of the multi-dimensional scaling plot and the Neighbour network reconstruction. We observed a moderate and weak population structure in Northern and Central-Southern breeds, respectively, with pairwise FST values between breeds ranging from 0.013 to 0.164 and 7.49 % of the total variance assigned to the between-breed level. Only 2.11 % of the variance explained the clustering of breeds into geographical groups (Northern, Central and Southern Italy and Islands). Conclusions: Our results indicate that the present-day genetic diversity of Italian goat populations was shaped by the combined effects of drift, presence or lack of gene flow and, to some extent, by the consequences of traditional management systems and recent demographic history. Our findings may constitute the starting point for the development of marker-assisted approaches, to better address future breeding and management policies in a species that is particularly relevant for the medium-and long-term sustainability of marginal regions

Assessing the spatial dependence of adaptive loci in 43 European and Western Asian goat breeds using AFLP markers

Background During the past decades, neutral DNA markers have been extensively employed to study demography, population genetics and structure in livestock, but less interest has been devoted to the evaluation of livestock adaptive potential through the identification of genomic regions likely to be under natural selection. Methodology/Principal findings Landscape genomics can greatly benefit the entire livestock system through the identification of genotypes better adapted to specific or extreme environmental conditions. Therefore we analyzed 101 AFLP markers in 43 European and Western Asian goat breeds both with Matsam software, based on a correlative approach (SAM), and with Mcheza and Bayescan, two FST based software able to detect markers carrying signatures of natural selection. Matsam identified four loci possibly under natural selection – also confirmed by FST-outlier methods – and significantly associated with environmental variables such as diurnal temperature range, frequency of precipitation, relative humidity and solar radiation. Conclusions/Significance These results show that landscape genomics can provide useful information on the environmental factors affecting the adaptive potential of livestock living in specific climatic conditions. Besides adding conservation value to livestock genetic resources, this knowledge may lead to the development of novel molecular tools useful to preserve the adaptive potential of local breeds during genetic improvement programs, and to increase the adaptability of industrial breeds to changing environments

Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer

DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6x10-5) and rs2155388 in CHEK1 (p=3.1x10-6), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

Terragni tra Como e Roma: modernità e città storica Como ve Roma Arasında Terragni: Modernizm ve Tarihi Şehir

Questo testo si propone di analizzare alcuni progetti di Giuseppe Terragni per Como e per Roma, in un periodo compreso tra il 1933 e il 1941. L’obiettivo è di evidenziare - seppure in un quadro di forte coerenza - i diversi modi seguiti dall’architetto nell’affrontare il tema del rapporto tra moderno e città storica

A cavallo della guerra

Il saggio disegna la metamorfosi della mappa del potere in architettura nel passaggio tra fascismo e post fascismo. Evidenzia in particolare gli elementi di continuit\ue0 espressi da alcune figue chiave come Piacentini, Giovannoni, Calza Bini, Foschini

Introduzione

Il testo introduce alla lettura dei 12 saggi raccolti nel volume, ne evidenzia i principali contenuti e l'originalit\ue0 offerta dai singoli saggi alla conoscenza storica delle architetture esaminate