Urine cadmium and urolithiasis: A systematic review and meta-analysis.

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 µg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01-1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 µg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02-1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure.

Safety assessment, radioiodination and preclinical evaluation of antinuclear antibody as novel medication for prostate cancer in mouse xenograft model.

This study aims to provide in vitro and in vivo data to support the utilization of antinuclear antibodies (ANAs) as novel tools for the diagnosis and treatment of prostate cancers. The hematological, biochemical, and histological toxicities of ANAs were assessed at the doses of 5 and 50 µg per mouse. Radiolabeling study was then conducted with ANA and 131I using the chloramine T method, and the biodistribution and treatment efficacy were subsequently investigated in a PC3 xenograft model. No changes in clinical behavior or signs of intoxication, necrosis, or malignancy were observed in ANA-treated mice. 131I-ANA was obtained in very high yield and radiochemical purity, at 94.97 ± 0.98% and 98.56 ± 0.29%, respectively. They achieved immunoreactivity fraction of 0.841 ± 0.17% with PC-3 cells. Levels of radiolabeled ANAs were 1.15-10.14 times higher in tumor tissues than in other examined organs at 24 h post-injection. The tumor growth inhibition rates were 28.33 ± 5.01% in PC3 xenografts mice treated with 131I-ANAs compared with controls and a nearly twofold improvement in median survival was observed. These results demonstrate that radioimmunotherapy of radiolabeled natural ANAs may be an effective treatment for prostate tumors.

Trends in genetic diversity and the effect of inbreeding in American Angus cattle under genomic selection.

BACKGROUND: While the adoption of genomic evaluations in livestock has increased genetic gain rates, its effects on genetic diversity and accumulation of inbreeding have raised concerns in cattle populations. Increased inbreeding may affect fitness and decrease the mean performance for economically important traits, such as fertility and growth in beef cattle, with the age of inbreeding having a possible effect on the magnitude of inbreeding depression. The purpose of this study was to determine changes in genetic diversity as a result of the implementation of genomic selection in Angus cattle and quantify potential inbreeding depression effects of total pedigree and genomic inbreeding, and also to investigate the impact of recent and ancient inbreeding. RESULTS: We found that the yearly rate of inbreeding accumulation remained similar in sires and decreased significantly in dams since the implementation of genomic selection. Other measures such as effective population size and the effective number of chromosome segments show little evidence of a detrimental effect of using genomic selection strategies on the genetic diversity of beef cattle. We also quantified pedigree and genomic inbreeding depression for fertility and growth. While inbreeding did not affect fertility, an increase in pedigree or genomic inbreeding was associated with decreased birth weight, weaning weight, and post-weaning gain in both sexes. We also measured the impact of the age of inbreeding and found that recent inbreeding had a larger depressive effect on growth than ancient inbreeding. CONCLUSIONS: In this study, we sought to quantify and understand the possible consequences of genomic selection on the genetic diversity of American Angus cattle. In both sires and dams, we found that, generally, genomic selection resulted in decreased rates of pedigree and genomic inbreeding accumulation and increased or sustained effective population sizes and number of independently segregating chromosome segments. We also found significant depressive effects of inbreeding accumulation on economically important growth traits, particularly with genomic and recent inbreeding.

Development of a genetic evaluation for hair shedding in American Angus cattle to improve thermotolerance.

BACKGROUND: Heat stress and fescue toxicosis caused by ingesting tall fescue infected with the endophytic fungus Epichloë coenophiala represent two of the most prevalent stressors to beef cattle in the United States and cost the beef industry millions of dollars each year. The rate at which a beef cow sheds her winter coat early in the summer is an indicator of adaptation to heat and an economically relevant trait in temperate or subtropical parts of the world. Furthermore, research suggests that early-summer hair shedding may reflect tolerance to fescue toxicosis, since vasoconstriction induced by fescue toxicosis limits the ability of an animal to shed its winter coat. Both heat stress and fescue toxicosis reduce profitability partly via indirect maternal effects on calf weaning weight. Here, we developed parameters for routine genetic evaluation of hair shedding score in American Angus cattle, and identified genomic loci associated with variation in hair shedding score via genome-wide association analysis (GWAA). RESULTS: Hair shedding score was moderately heritable (h2 = 0.34 to 0.40), with different repeatability estimates between cattle grazing versus not grazing endophyte-infected tall fescue. Our results suggest modestly negative genetic and phenotypic correlations between a dam's hair shedding score (lower score is earlier shedding) and the weaning weight of her calf, which is one metric of performance. Together, these results indicate that economic gains can be made by using hair shedding score breeding values to select for heat-tolerant cattle. GWAA identified 176 variants significant at FDR < 0.05. Functional enrichment analyses using genes that were located within 50 kb of these variants identified pathways involved in keratin formation, prolactin signalling, host-virus interaction, and other biological processes. CONCLUSIONS: This work contributes to a continuing trend in the development of genetic evaluations for environmental adaptation. Our results will aid beef cattle producers in selecting more sustainable and climate-adapted cattle, as well as enable the development of similar routine genetic evaluations in other breeds.

Predicting Growth and Carcass Traits in Swine Using Microbiome Data and Machine Learning Algorithms.

In this paper, we evaluated the power of microbiome measures taken at three time points over the growth test period (weaning, 15 and 22 weeks) to foretell growth and carcass traits in 1039 individuals of a line of crossbred pigs. We measured prediction accuracy as the correlation between actual and predicted phenotypes in a five-fold cross-validation setting. Phenotypic traits measured included live weight measures and carcass composition obtained during the trial as well as at slaughter. We employed a null model excluding microbiome information as a baseline to assess the increase in prediction accuracy stemming from the inclusion of operational taxonomic units (OTU) as predictors. We further contrasted performance of models from the Bayesian alphabet (Bayesian Lasso) as well machine learning approaches (Random Forest and Gradient Boosting) and semi-parametric kernel models (Reproducing Kernel Hilbert space). In most cases, prediction accuracy increased significantly with the inclusion of microbiome data. Accuracy was more substantial with the inclusion of microbiome information taken at weeks 15 and 22, with values ranging from approximately 0.30 for loin traits to more than 0.50 for back fat. Conversely, microbiome composition at weaning resulted in most cases in marginal gains of prediction accuracy, suggesting that later measures might be more useful to include in predictive models. Model choice affected predictions marginally with no clear winner for any model/trait/time point. We, therefore, suggest average prediction across models as a robust strategy in fitting microbiome information. In conclusion, microbiome composition can effectively be used as a predictor of growth and composition traits, particularly for fatness traits. The inclusion of OTU predictors could potentially be used to promote fast growth of individuals while limiting fat accumulation. Early microbiome measures might not be good predictors of growth and OTU information might be best collected at later life stages. Future research should focus on the inclusion of both microbiome as well as host genome information in predictions, as well as the interaction between the two. Furthermore, the influence of the microbiome on feed efficiency as well as carcass and meat quality should be investigated.

Host contributes to longitudinal diversity of fecal microbiota in swine selected for lean growth.

BACKGROUND: In pigs, gut bacteria have been shown to play important roles in nutritional, physiological, and immunological processes in the host. However, the contribution of their metagenomes or part of them, which are normally reflected by fragments of 16S rRNA-encoding genes, has yet to be fully investigated. RESULTS: Fecal samples, collected from a population of crossbred pigs at three time points, including weaning, week 15 post weaning (hereafter "week 15"), and end-of-feeding test (hereafter "off-test"), were used to evaluate changes in the composition of the fecal microbiome of each animal over time. This study used 1205, 1295, and 1283 samples collected at weaning, week 15, and off-test, respectively. There were 1039 animals that had samples collected at all three time points and also had phenotypic records on back fat thickness (BF) and average daily body weight gain (ADG). Firmicutes and Bacteroidetes were the most abundant phyla at all three time points. The most abundant genera at all three time points included Clostridium, Escherichia, Bacteroides, Prevotella, Ruminococcus, Fusobacterium, Campylobacter, Eubacterium, and Lactobacillus. Two enterotypes were identified at each time point. However, only enterotypes at week 15 and off-test were significantly associated with BF. We report herein two novel findings: (i) alpha diversity and operational taxonomic unit (OTU) richness were moderately heritable at week 15, h2 of 0.15 ± 0.06 to 0.16 ± 0.07 and 0.23 ± 0.09 to 0.26 ± 0.08, respectively, as well as at off-test, h2 of 0.20 ± 0.09 to 0.33 ± 0.10 and 0.17 ± 0.08 to 0.24 ± 0.08, respectively, whereas very low heritability estimates for both measures were detected at weaning; and (ii) alpha diversity at week 15 had strong and negative genetic correlations with BF, - 0.53 ± 0.23 to - 0.45 ± 0.25, as well as with ADG, - 0.53 ± 0.32 to - 0.53 ± 0.29. CONCLUSIONS: These results are important for efforts to genetically improve the domesticated pig because they suggest fecal microbiota diversity can be used as an indicator trait to improve traits that are expensive to measure.

Association analysis for feed efficiency traits in beef cattle using preserved haplotypes.

This study reports a genome wide scan for chromosome regions and their haplotypes that significantly associated with average daily gain (ADG), dry matter intake (DMI), and residual feed intake (RFI) in beef cattle. The study used data from 597 Angus, 450 Charolais, and 616 crossbred beef cattle, and the Illumina Bovine SNP50 beadchip. Extended haplotype homozygosity was used to identify chromosome regions that had been recently selected for in the three groups of animals. Such regions in the crossbreds were tested for association with ADG, DMI, and RFI. At false discovery rates of 5% and 10%, there were six and eight chromosome regions showing significant associations with the traits, respectively. At nominal significance levels (at least P < 0.05), 23 regions with a total number of 31 haplotypes were found significantly associated with at least one of the three traits. The proportion of phenotypic variance explained by these 23 regions varied depending on the trait; the highest proportion for ADG, DMI, and RFI was 13.50%, 9.92%, and 2.64%, respectively. Most of the haplotypes affected single traits, except for GAA (BTA4), GCG (BTA7), and TAGT (BTA12) that affected multiple traits. Thirty-six quantitative trait loci for 16 production traits, from the current literature, covered fully or in part the 23 chromosome regions. The findings from this study might be an important contribution to the current knowledge of the beef cattle genome and to the effective identification of causative genes associated with important traits in cattle.

Genome-wide association analyses for carcass quality in crossbred beef cattle.

BACKGROUND: Genetic improvement of beef quality will benefit both producers and consumers, and can be achieved by selecting animals that carry desired quantitative trait nucleotides (QTN), which result from intensive searches using genetic markers. This paper presents a genome-wide association approach utilizing single nucleotide polymorphisms (SNP) in the Illumina BovineSNP50 BeadChip to seek genomic regions that potentially harbor genes or QTN underlying variation in carcass quality of beef cattle.This study used 747 genotyped animals, mainly crossbred, with phenotypes on twelve carcass quality traits, including hot carcass weight (HCW), back fat thickness (BF), Longissimus dorsi muscle area or ribeye area (REA), marbling scores (MRB), lean yield grade by Beef Improvement Federation formulae (BIFYLD), steak tenderness by Warner-Bratzler shear force 7-day post-mortem (LM7D) as well as body composition as determined by partial rib (IMPS 103) dissection presented as a percentage of total rib weight including body cavity fat (BDFR), lean (LNR), bone (BNR), intermuscular fat (INFR), subcutaneous fat (SQFR), and total fat (TLFR). RESULTS: At the genome wide level false discovery rate (FDR < 10%), eight SNP were found significantly associated with HCW. Seven of these SNP were located on Bos taurus autosome (BTA) 6. At a less stringent significance level (P < 0.001), 520 SNP were found significantly associated with mostly individual traits (473 SNP), and multiple traits (47 SNP). Of these significant SNP, 48 were located on BTA6, and 22 of them were in association with hot carcass weight. There were 53 SNP associated with percentage of rib bone, and 12 of them were on BTA20. The rest of the significant SNP were scattered over other chromosomes. They accounted for 1.90 - 5.89% of the phenotypic variance of the traits. A region of approximately 4 Mbp long on BTA6 was found to be a potential area to harbor candidate genes influencing growth. One marker on BTA25 accounting for 2.67% of the variation in LM7D may be worth further investigation for the improvement of beef tenderness. CONCLUSION: This study provides useful information to further assist the identification of chromosome regions and subsequently genes affecting carcass quality traits in beef cattle. It also revealed many SNP that acted pleiotropically to affect carcass quality. This knowledge is important in selecting subsets of SNP to improve the performance of beef cattle.

Linkage disequilibrium in Angus, Charolais, and Crossbred beef cattle.

Linkage disequilibrium (LD) and the persistence of its phase across populations are important for genomic selection as well as fine scale mapping of quantitative trait loci (QTL). However, knowledge of LD in beef cattle, as well as the persistence of LD phase between crossbreds (C) and purebreds, is limited. The objective of this study was to understand the patterns of LD in Angus (AN), Charolais (CH), and C beef cattle based on 31,073, 32,088, and 33,286 SNP in each population, respectively. Amount of LD decreased rapidly from 0.29 to 0.23 to 0.19 in AN, 0.22 to 0.16 to 0.12 in CH, 0.21 to 0.15 to 0.11 in C, when the distance range between markers changed from 0-30 kb to 30-70 kb and then to 70-100 kb, respectively. Breeds and chromosomes had significant effects (P < 0.001) on LD decay. There was significant interaction between breeds and chromosomes (P < 0.001). Correlations of LD phase were high between C and AN (0.84), C and CH (0.81), as well as between AN and CH (0.77) for distances less than or equal to 70 kb. These dropped when the distance increased. Estimated effective population sizes for AN and CH were 207 and 285, respectively, for 10 generations ago. Given a useful LD of at least 0.3 between pairs of SNPs, the LD phase between any pair of the three breed groups was highly persistent. The current SNP density would allow the capture of approximately 49% of useful LD between SNP and marker QTL in AN, and 38% in CH. A higher density SNP panel or redesign of the current panel is needed to achieve more of useful LD for the purpose of genomic selection beef cattle.