Use of partial least squares regression to impute SNP genotypes in Italian Cattle breeds

Background The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used. Methods Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content. Results In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip. Conclusions Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available

Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability

Multiple-breed genomic evaluation by principal component analysis in small size populations

In this study, the effects of breed composition and predictor dimensionality on the accuracy of direct genomic values (DGV) in a multiple breed (MB) cattle population were investigated. A total of 3559 bulls of three breeds were genotyped at 54 001 single nucleotide polymorphisms: 2093 Holstein (H), 749 Brown Swiss (B) and 717 Simmental (S). DGV were calculated using a principal component (PC) approach for either single (SB) or MB scenarios. Moreover, DGV were computed using all SNP genotypes simultaneously with SNPBLUP model as comparison. A total of seven data sets were used: three with a SB each, three with different pairs of breeds (HB, HS and BS), and one with all the three breeds together (HBS), respectively. Editing was performed separately for each scenario. Reference populations differed in breed composition, whereas the validation bulls were the same for all scenarios. The number of SNPs retained after data editing ranged from 36 521 to 41 360. PCs were extracted from actual genotypes. The total number of retained PCs ranged from 4029 to 7284 in Brown Swiss and HBS respectively, reducing the number of predictors by about 85% (from 82% to 89%). In all, three traits were considered: milk, fat and protein yield. Correlations between deregressed proofs and DGV were used to assess prediction accuracy in validation animals. In the SB scenarios, average DGV accuracy did not substantially change when either SNPBLUP or PC were used. Improvement of DGV accuracy were observed for some traits in Brown Swiss, only when MB reference populations and PC approach were used instead of SB-SNPBLUP (+10% HBS, +16%HB for milk yield and +3% HBS and +7% HB for protein yield, respectively). With the exclusion of the abovementioned cases, similar accuracies were observed using MB reference population, under the PC or SNPBLUP models. Random variation owing to sampling effect or size and composition of the reference population may explain the difficulty in finding a defined pattern in the results

Design of fluorinated stealth poly(ε-caprolactone) nanocarriers

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Assessment of increased glomerular permeability associated with recurrent focal segmental glomerulosclerosis using an in vitro model of the glomerular filtration barrier

The presence of circulating permeability factors (cPFs) has been hypothesized to be associated with recurrence of focal segmental glomerulosclerosis (rFSGS) in renal allografts. The available methods to detect cPFs are complex, not easily repeatable and inappropriate to represent the anatomical characteristics of the three-layer glomerular filtration barrier (GFB). Here we describe a novel method which measures the permeability to bovine serum albumin (BSA) through a three-layer device (3LD). The 3 layers comprise: (1) conditionally immortalized human podocytes (HCiPodo), (2) collagen type IV coated porous membrane and (3) human glomerular endothelial cells (HCiGEnC). Using this method, we found that sera from all rFSGS patients increased albumin permeability, while sera from non recurrent (nrFSGS) and genetic (gFSGS) forms of FSGS did not. The mechanisms underlying the increase of albumin permeability are probably due to endothelial cell damage as an initial event, which was demonstrated by the decrease of Platelet endothelial cell adhesion molecule (PECAM-1 or CD31), while the podocytes’ expressions of synaptopodin and podocin were normal. Furthermore, we also found that the plasmapheretic treatment (PPT) eliminated the effect of increasing BSA permeability in sera from rFSGS patients. These preliminary data suggest that our in vitro GFB model could not only be useful in predicting the recurrence of FSGS after renal transplantation (RTx), but also be a valuable in vitro model to study podocyte and endothelial cell biology

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services