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Background: A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the periparturient period., Methods: Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 weeks preceding calving (75 and 125 % of estimated requirements). Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44 K Bovine (V2) Microarray chip. The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis., Results: The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance (1071 vs 310, over the entire transition period) indicates that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. Altered carbohydrate and amino acid metabolism suggest a greater and more prolonged negative energy balance postpartum in BCS5 cows overfed prepartum. This is supported by opposite effects of prepartum feeding in BCS4 compared with BCS5 cows in pathways encompassing amino acid, vitamin, and co-factor metabolism. The prepartum feed restriction ameliorates the metabolic adaptation to the onset of lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seem to better adapt when overfed. Alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 and overfed BCS4 cows. Furthermore, IPA network analysis suggests liver damage in feed-restricted thin cows, likely due to metabolic overload., Conclusion: Overall, the data support the hypothesis that overfeeding in late-pregnancy should be limited to underconditioned cows, while cows with optimal degree of body condition should be maintained on an energy-restricted diet.

Genome-wide association studies have identified SNPs reproducibly associated with type 2 diabetes (T2D). We examined the effect of genetic predisposition to T2D on insulin sensitivity and secretion using detailed phenotyping in overweight individuals with no diagnosis of T2D. Furthermore, we investigated whether this genetic predisposition modifies the responses in beta-cell function and insulin sensitivity to a 24-week dietary intervention. We genotyped 25 T2D-associated SNPs in 377 white participants from the RISCK study. Participants underwent an IVGTT prior to and following a dietary intervention that aimed to lower saturated fat intake by replacement with monounsaturated fat or carbohydrate. We composed a genetic predisposition score (T2D-GPS) by summing the T2D risk-increasing alleles of the 25 SNPs and tested for association with insulin secretion and sensitivity at baseline, and with the change in response to the dietary intervention. At baseline, a higher T2D-GPS was associated with lower acute insulin secretion (AIRg 4% lower/risk allele, P = 0.006) and lower insulin secretion for a given level of insulin sensitivity, assessed by the disposition index (DI 5% lower/risk allele, P = 0.002), but not with insulin sensitivity (Si). T2D-GPS did not modify changes in insulin secretion, insulin sensitivity or the disposition index in response to the dietary interventions to lower saturated fat. Participants genetically predisposed to T2D have an impaired ability to compensate for peripheral insulin resistance with insulin secretion at baseline, but this does not modify the response to a reduction in dietary saturated fat through iso-energetic replacement with carbohydrate or monounsaturated fat.

Background: Bohler's angle and the crucial angle of Gissane can be used to assess calcaneal fractures. While the normal adult values of these angles are widely known, the normal paediatric values have not yet been established. Our aim is to investigate Bohler's angle and the crucial angle of Gissane in a paediatric population and establish normal paediatric reference values., Method: We measured Bohler's angle and the crucial angle of Gissane using normal plain ankle radiographs of 763 patients from birth to 14 years of age completed over a five year period from July 2003 to June 2008., Results: In our paediatric study group, the mean Bohler's angle was 35.2 degrees and the mean crucial angle of Gissane was 111.3 degrees. In an adult comparison group, the mean Bohler's angle was 39.2 degrees and the mean crucial angle of Gissane was 113.8 degrees. The differences in Bohler's angle and the crucial angle of Gissane between these two groups were statistically significant., Conclusion: We have presented the normal values of Bohler's angle and the crucial angle of Gissane in a paediatric population. These values may provide a useful comparison to assist with the management of the paediatric calcaneal fracture.

Background: A large proportion of pregnancy losses occur during the pre-implantation period, when the developing embryo is elongating rapidly and signalling its presence to the maternal system. The molecular mechanisms that prevent luteolysis and support embryo survival within the maternal environment are not well understood. To gain a more complete picture of these molecular events, genome-wide transcriptional profiles of reproductive day 17 endometrial tissue were determined in pregnant and cyclic Holstein-Friesian dairy cattle., Results: Microarray analyses revealed 1,839 and 1,189 differentially expressed transcripts between pregnant and cyclic animals (with > or = 1.5 fold change in expression; P-value < 0.05, MTC Benjamini-Hochberg) in caruncular and intercaruncular endometrium respectively. Gene ontology and biological pathway analysis of differentially expressed genes revealed enrichment for genes involved in interferon signalling and modulation of the immune response in pregnant animals., Conclusion: The maternal immune system actively surveys the uterine environment during early pregnancy. The embryo modulates this response inducing the expression of endometrial molecules that suppress the immune response and promote maternal tolerance to the embryo. During this period of local immune suppression, genes of the innate immune response (in particular, antimicrobial genes) may function to protect the uterus against infection.

Background: Quantitative real-time PCR gene expression results are generally normalised using endogenous control genes. These reference genes should be expressed at a constant level across all sample groups in a study, and should not be influenced by study treatments or conditions. There has been no systematic investigation of endogenous control genes for bovine endometrium to date. The suitability of both commonly used and novel endogenous control genes was evaluated in this study, with the latter being selected from stably expressed transcripts identified through microarray analysis of bovine endometrium. Fifteen candidate endogenous control genes were assessed across different tissue subtypes in pregnant and cycling Holstein-Friesian dairy cows from two divergent genetic backgrounds., Results: The expression profiles of five commonly used endogenous control genes (GAPDH, PPIA, RPS9, RPS15A, and UXT) and 10 experimentally derived candidate endogenous control genes (SUZ12, C2ORF29, ZNF131, ACTR1A, HDAC1, SLC30A6, CNOT7, DNAJC17, BBS2, and RANBP10) were analysed across 44 samples to determine the most stably expressed gene. Gene stability was assessed using the statistical algorithms GeNorm and Normfinder. All genes presented with low overall variability (0.87 to 1.48% CV of Cq). However, when used to normalise a differentially expressed gene (oxytocin receptor - OXTR) in the samples, the reported relative gene expression levels were significantly affected by the control gene chosen. Based on the results of this analysis, SUZ12 is proposed as the most appropriate control gene for use in bovine endometrium during early pregnancy or the oestrus cycle., Conclusion: This study establishes the suitability of novel endogenous control genes for comparing expression levels in endometrial tissues of pregnant and cycling bovines, and demonstrates the utility of microarray analysis as a method for identifying endogenous control gene candidates.