Early life jumping traits: Are they good proxies for success in show jumping competitions in Belgian warmblood horses?

The main goal of the Belgian Warmblood horse studbook (BWP) is to breed successful competition horses, with emphasis on show jumping. However, competition results are only available later in life and competition traits are lowly heritable. Hence, the use of phenotypes that record performance-related traits at an early life stage could help increase genetic progress. In this study, we evaluated the potential of eleven linear scored early life jumping traits assessed during jumping in freedom (2-5 years old) or under the saddle (4-6 years old) as proxies for later success in show jumping competitions. To this end, we estimated their heritabilities and genetic correlations with the competition trait, adjusted fence height, by using 2170 free jumping records, 1588 jumping under saddle records, 674,527 show jumping competition records and almost 81,000 informative horses in the pedigree. As participation of young horses in these contests is on a voluntary basis, a pre-selection most probably exists. To verify this hypothesis, we investigated the association between participation to young horse contests and participation to show jumping competitions later on (called here start status phenotype). We also estimated heritabilities for "start status in free jumping contest", "start status in jumping under saddle contest" and "start status in free jumping or jumping under saddle contest" by fitting threshold models. Furthermore, we calculated genetic correlations between these traits and adjusted fence height and calculated the correlations between EBVs for start status in young horse contests and EBVs for success in competitions. Estimated heritabilities of early life jumping traits ranged between 0.05 and 0.30. Their genetic correlations with adjusted fence height were moderate to high (rg = 0.37-0.63). Relatively more horses that participated in young horse contests competed later on compared to horses that did not participate in young horse contests (p-value < 0.001). They were also significantly more successful in show jumping competitions. Furthermore, start status in young horse contests was moderately heritable in BWP horses (h2 = 0.56-0.65) and moderately to highly correlated with later success in competitions (rg = 0.30-0.77). Hence, we showed that ELJ traits are good proxies for later success in competitions and that a pre-selection of horses occurs in young horse contests. It is suggested to stimulate participation to young horse contests to achieve a more representative sample of the population. Early life jumping traits can therefore optimize the genetic progress for show jumping performance.

Molecular insights on skewing of sex ratio in rabbits (Oryctolagus cuniculus) supplemented with dietary calcium and magnesium.

The effect of dietary calcium (Ca) and magnesium (Mg) supplementation on serum biochemical parameters, steroid hormones, gene expression, and the sex ratio was investigated in female New Zealand white rabbits. A total of 25 rabbits were allocated into five treatment groups: The control group was fed with regular pellet feed, whereas, treatment groups were supplemented with Ca and Mg: T1 (0.40% and 0.01%), T2 (0.60% and 0.02%), T3 (0.80% and 0.03%) and T4 (1.00% and 0.04%), respectively. The rabbits were subjected to three breeding cycles. The T3 group skewed towards females (65.33%) from all three breeding. There was elevated Ca concentration in T3 (15.26 ± 0.77 mg dL-1) and T4 (15.61 ± 0.82 mg dL-1) groups compared to the control. The concentration of estradiol was significantly high in T3 and T4 groups at 0.5 days post-coitus (dpc) and T2, T3 and T4 groups at 21dpc. Testosterone was significantly high in T4 group at 0.50 dpc and T2 and T4 group at 21dpc. The expression of 13 genes was studied in the oviduct. Genes such as OVGP1, CCT4, ANXA2 and TLR4 were up-regulated and positively correlated with the female sex ratio. The molecular functions and pathways of up-regulated genes were suggestive of their role in fertilization such as sperm selection, sperm storage, immune regulation, implantation and early embryonic development. The variations in the serum electrolytes, steroid hormones and gene expression might have an impact on the skewing process.

A double pre-selection method for natural background levels assessment in coastal groundwater bodies.

To evaluate the chemical status of groundwater bodies (GWB) according to the European Groundwater Directive, EU Member States are required to take into account natural background levels (NBLs) where needed. Assessing the NBLs in coastal GWBs is complicated by seawater intrusion which can be amplified by groundwater withdrawals increasing the salinization of such groundwater systems. This paper proposes a new method for the NBLs assessment in coastal areas based on a double pre-selection (PS) with fixed/dynamic limits. A case study in the Apulia region, located in southeastern Italy, is proposed, where we investigated four adjacent GWBs which form the complex karst, fractured Murgia aquifer, hosted in the Jurassic-Cretaceous carbonate platform, bounded by two seas and sustained by saltwater of marine intrusion in the coastal areas. Data related to 139 monitoring stations (MSs) of the regional groundwater monitoring network were used. The first PS, "static", based on a fixed limit of anthropogenic contamination markers (NO3 and NH4), allows for the elimination of MSs impacted by human activities. On these, the second PS, "dynamic", based on the identification of Cl anomalous values, allows for the identification of additional MSs affected by saline contamination. The residual dataset of MSs was used for the definition of NBLs of Cl, SO4, F and B. A statistical comparison with historical Cl observations finally allowed us to verify if the salinity of current groundwater is representative of pristine conditions. The calculated NBLs of salinity parameters are higher for the two coastal GWBs, with chloride values between 0.8 and 2 mg/L. Conversely, fluorides always show very low NBLs. The double PS approach seems more effective for NBLs calculation in coastal aquifers affected by saline contamination, where the use of a fixed Cl limit fails. It may respond to the international needs for a standardized procedure for NBL assessment.

Natural background levels in groundwater in the Pearl River Delta after the rapid expansion of urbanization: A new pre-selection method.

Establishment of natural background levels (NBL) of groundwater in urbanized areas such as the Pearl River Delta (PRD) is challenging. Pre-selection methods are the most common approaches for NBL assessment, but it will overestimate (or underestimate) contaminated groundwater in urbanized areas by using present pre-selection methods with empirical definite values because of complicated human activities. Unlike present pre-selection methods, this study aims to establish a new pre-selection method with the indicative of Cl/Br ratios to identify contaminated groundwaters with convincing evidences. Specifically, this new method consists of indicatives of the oxidation capacity and the Cl/Br ratio combining with contaminated-markers. In addition, factors controlling NBL of Cl and NO3 in groundwater in various hydrogeological units in the PRD were also discussed. Main procedures of this new method: contaminated-markers in various hydrogeological units are extracted by a hierarchical cluster analysis, thereby determining threshold values of Cl/Br ratios and Cl concentration in various hydrogeological units for identifying contaminated groundwater; After that, groundwater chemical datasets was selected by the oxidation capacity, and then tested by Grubbs' test until normal distributions. Groundwater Cl and NO3 concentrations in datasets before and after this new method are dependent and independent of urbanization levels, respectively, indicating that the new method is useful for groundwater NBL assessment in urbanized areas such as the PRD. Both the seawater intrusion and the diffusion of Cl from marine deposits are likely to be responsible for the much higher NBL-Cl in coastal-alluvial and marine aquifers than in other hydrogeological units. Groundwater Cl enrichment resulted from groundwater recharge and evaporation is mainly responsible for the higher NBL-Cl in alluvial-proluvial aquifers than in lacustrine aquifers, fissured aquifers, as well as karst aquifers. More than double times NBL-NO3 in alluvial-proluvial and fissured aquifers than in other hydrogeological units is probably attributed to more oxidizing conditions of their vadose zones and groundwaters.

Pre-selecting markers based on fixation index scores improved the power of genomic evaluations in a combined Yorkshire pig population.

Combining different swine populations in genomic prediction can be an important tool, leading to an increased accuracy of genomic prediction using single nucleotide polymorphism (SNP) chip data compared with within-population genomic. However, the expected higher accuracy of multi-population genomic prediction has not been realized. This may be due to an inconsistent linkage disequilibrium (LD) between SNPs and quantitative trait loci (QTL) across populations, and the weak genetic relationships across populations. In this study, we determined the impact of different genomic relationship matrices, SNP density and pre-selected variants on prediction accuracy using a combined Yorkshire pig population. Our objective was to provide useful strategies for improving the accuracy of genomic prediction within a combined population. Results showed that the accuracy of genomic best linear unbiased prediction (GBLUP) using imputed whole-genome sequencing (WGS) data in the combined population was always higher than that within populations. Furthermore, the use of imputed WGS data always resulted in a higher accuracy of GBLUP than the use of 80K chip data for the combined population. Additionally, the accuracy of GBLUP with a non-linear genomic relationship matrix was markedly increased (0.87% to 15.17% for 80K chip data, and 0.43% to 4.01% for imputed WGS data) compared with that obtained with a linear genomic relationship matrix, except for the prediction of XD population in the combined population using imputed WGS data. More importantly, the application of pre-selected variants based on fixation index (Fst) scores improved the accuracy of multi-population genomic prediction, especially for 80K chip data. For BLUP|GA (BLUP approach given the genetic architecture), the use of a linear method with an appropriate weight to build a weight-relatedness matrix led to a higher prediction accuracy compared with the use of only pre-selected SNPs for genomic evaluations, especially for the total number of piglets born. However, for the non-linear method, BLUP|GA showed only a small increase or even a decrease in prediction accuracy compared with the use of only pre-selected SNPs. Overall, the best genomic evaluation strategy for reproduction-related traits for a combined population was found to be GBLUP performed with a non-linear genomic relationship matrix using variants pre-selected from the 80K chip data based on Fst scores.

A multi-method approach for the assessment of natural background levels in groundwater.

The assessment of geochemical Natural Background Levels (NBLs) in groundwater, aims at distinguishing the naturally high levels of geogenic compounds from anthropogenic pollution. This is a fundamental issue in groundwater management, in particular when the concentration of inorganic compounds exceeds the threshold values set for the evaluation of the groundwater chemical status, as requested by environmental regulations. In this paper, we describe a new procedure that integrates the pre-selection method and statistical techniques, using the example of two case studies. The pre-selection aims to identify suitable groundwater samples for the NBLs assessment. The nitrate concentration threshold, for the removal of the groundwater samples affected by human activities, is established locally through different graphical and statistical approaches. Then, the statistical distribution of each compound is analyzed and the outliers are identified. Normality tests on the datasets allow one to select the most appropriate value, e.g. one percentile, to be adopted as NBL within the data distribution. In the selected case studies, we have defined the NBLs for As, F, Mn, Fe and SO4. The two sites are part of a volcanic-sedimentary aquifer in central Italy, where the geochemical background is frequently well above the standards for human consumption. The results of the simple and easily reproducible pre-selection method are strengthened by integration with statistical techniques, notably in selecting the appropriate percentile. New criteria are suggested for the choice of the nitrate threshold to be used for the pre-selection of uncontaminated samples.

Comparison of performance and metabolism from late pregnancy to early lactation in dairy cows with elevated v. normal body condition at dry-off.

Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and ß-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3'-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.

Challenges and strategies in anti-cancer nanomedicine development: An industry perspective.

Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. We should evolve our nanomedicine development strategies to build the patient and disease into the line of sight from the outset. The success of small molecule targeted therapies has been significantly improved by employing a specific decision-making framework, such as AstraZeneca's 5R principle: right target/efficacy, right tissue/exposure, right safety, right patient, and right commercial potential. With appropriate investment and collaboration to generate a platform of evidence supporting the end clinical application, a similar framework can be established for enhancing nanomedicine translation and performance. Building informative data packages to answer these questions requires the following: (I) an improved understanding of the heterogeneity of clinical cancers and of the biological factors influencing the behaviour of nanomedicines in patient tumours; (II) a transition from formulation-driven research to disease-driven development; (III) the implementation of more relevant animal models and testing protocols; and (IV) the pre-selection of the patients most likely to respond to nanomedicine therapies. These challenges must be overcome to improve (the cost-effectiveness of) nanomedicine development and translation, and they are key to establishing superior therapies for patients.

Genomic Selection Using Extreme Phenotypes and Pre-Selection of SNPs in Large Yellow Croaker (Larimichthys crocea).

Genomic selection (GS) is an effective method to improve predictive accuracies of genetic values. However, high cost in genotyping will limit the application of this technology in some species. Therefore, it is necessary to find some methods to reduce the genotyping costs in genomic selection. Large yellow croaker is one of the most commercially important marine fish species in southeast China and Eastern Asia. In this study, genotyping-by-sequencing was used to construct the libraries for the NGS sequencing and find 29,748 SNPs in the genome. Two traits, eviscerated weight (EW) and the ratio between eviscerated weight and whole body weight (REW), were chosen to study. Two strategies to reduce the costs were proposed as follows: selecting extreme phenotypes (EP) for genotyping in reference population or pre-selecting SNPs to construct low-density marker panels in candidates. Three methods of pre-selection of SNPs, i.e., pre-selecting SNPs by absolute effects (SE), by single marker analysis (SMA), and by fixed intervals of sequence number (EL), were studied. The results showed that using EP was a feasible method to save the genotyping costs in reference population. Heritability did not seem to have obvious influences on the predictive abilities estimated by EP. Using SMA was the most feasible method to save the genotyping costs in candidates. In addition, the combination of EP and SMA in genomic selection also showed good results, especially for trait of REW. We also described how to apply the new methods in genomic selection and compared the genotyping costs before and after using the new methods. Our study may not only offer a reference for aquatic genomic breeding but also offer a reference for genomic prediction in other species including livestock and plants, etc.

Cross-border reprogenetic services.

The purpose of this review is to synthesize the current knowledge on the international movement of patients and biopsied embryo cells for pre-implantation genetic diagnosis and its different applications. Thus far, few attempts have been made to identify the specific nature of this phenomenon called 'cross-border reprogenetic services'. There is scattered evidence, both empirical and speculative, suggesting that these services raise major issues in terms of service provision, risks for patients and the children-to-come, the legal liabilities of physicians, as well as social justice. To compile this evidence, this review uses the narrative overview protocol combined with thematic analysis. Five major themes have emerged from the literature at the conjunction of cross-border treatments and reprogenetics: 'scope', 'scale', 'motivations', 'concerns', and 'governance'. Similar themes have already been observed in the case of other medical tourism activities, but this review highlights their singularity with reprogenetic services. It emphasizes the diagnostic and autologous feature of reprogenetics, the constant risk of misdiagnosis, the restriction on certain tests for medically controversial conditions, and the uncertain accessibility of genetic counseling in cross-border settings.

Desempenho agroindustrial de cultivares de cana-de-açúcar na zona da mata litoral sul de Pernambuco / Agroindustrial performance of sugar cane cultivars in the coastal-forest zone of Pernambuco

Objetivou-se, neste trabalho, avaliar a variabilidade genética de alguns caracteres da planta e o desempenho agroindustrial em cultivares de cana-de-açúcar. O delineamento experimental foi o de blocos casualizados, com quatro blocos e dezesseis cultivares. As parcelas foram formadas por cinco sulcos de 8,0 m de comprimento, espaçados de 1,0 m, caracterizando uma área útil de 40 m². Foram avaliadas as variáveis toneladas de cana por hectare (TCH), toneladas de pol por hectare (TPH), pol na cana (PC), fibra por cento cana (FIB), brix na cana (BC) e pureza na cana (PUR). O TCH é o componente mais influenciado pelos ciclos de colheita da lavoura de cana-de-açúcar e o menos expressivo para os demais caracteres estudados. As variáveis TCH e TPH refletiram a maior parte da variação fenotípica observada devida às causas genéticas, indicando êxito na seleção no melhoramento desses caracteres. Os genótipos SP78-4764, SP86-0621 e SP86-127 demonstraram potencial produtivo do ponto de vista agroindustrial. O efeito de ciclo de colheita da cana foi altamente significativo indicando o comportamento específico entre as cultivares durante os cortes da cana.

The aim of this work was to evaluate the genetic variability of some characters of the plant and the agroindustrial performance of sugar cane cultivars. The experimental design was the complete randomized blocks with four replications and 16 cultivars, being four of them used as check varieties. The plots were formed by five furrows of 8.0 m length, spaced 1.0 m, characterizing a useful area of 40 m². The variables evaluated were the tons of cane per hectare (TCH), tons of pol per hectare (TPH), pol in the cane (PC), percent cane fiber (FIB), brix in the cane (BC) and purity in the cane (PUR). The TCH is the component most influenced by the harvest cycles of the sugar cane farming and the least expressive for the other studied characters. The variables TCH and TPH reflected most of the phenotypic variation observed due to genetic causes, indicating success in the selection for the improvement of these characters. The genotypes SP78-4764, SP86-0621, and SP86-127 demonstrated productive potential from the agroindustrial point of view. The effect of the cane cut cycle was highly significant, indicating specific behaviors among the cultivars during the cane harvest.

A deterministic simulation study of embryo marker-assisted selection for age at first calving in Nellore (Bos indicus) beef cattle

We used deterministic simulation of four alternative multiple ovulation and embryo manipulation (MOET) closed nucleus schemes to investigate the benefits of using marker-assisted selection (MAS) of Nellore (Bos indicus) beef cattle embryos prior to transplantation to reduce the age at first calving (AFC). We found that MAS resulted in increased genetic gain as compared to selection without AFC quantitative trait loci (AFC-QTL) information. With single-stage selection the genetic response (GR) increased as follows: GR = 0.68 percent when the AFC-QTL explained 0.02 of the AFC additive genetic variance (sigma2A); GR = 1.76 percent for AFC-QTL explaining 0.05 sigma2A; GR = 3.7 percent for AFC-QTL explaining 0.1 sigma2A; and GR = 55.76 percent for AFC-QTL explaining 0.95 sigma2A. At the same total selected proportion, two-stage selection resulted in less genetic gain than single stage MAS at two-years of age. A single stage selection responses of > 95 percent occurred with pre-selected proportions of 0.4 (0.1 sigma2A explained by AFC-QTL), 0.2 (0.3 sigma2A explained by AFC-QTL) and 0.1 (0.5 sigma2A explained by AFC-QTL), indicating that the combined use of MAS and pre-selection can substantially reduce the cost of keeping recipient heifers in MOET breeding schemes. When the number of recipients was kept constant, the benefit of increasing embryo production was greater for the QTL explaining a higher proportion of the additive genetic variance. However this advantage had a diminishing return especially for QTL explaining a small proportion of the additive genetic variance. Thus, marker assisted selection of embryos can be used to achieve increased genetic gain or a similar genetic response at reduced expense by decreasing the number of recipient cows and number of offspring raised to two-years of age.