The objective was to estimate genetic parameters of performance and resilience of growing pigs under disease. Data were from 3,139 Yorkshire x Landrace wean-to-finish pigs that were exposed to a natural polymicrobial disease challenge that was established by entering naturally infected animals into a nursery barn, targeting various viral and bacterial diseases. The challenge was maintained by entering batches of 60 to 75 healthy nursery pigs every 3 weeks in a continuous flow system. Traits analyzed included average daily gain (ADG), feed intake (ADFI), and duration (ADFD), feed conversion ratio (FCR), residual feed intake (RFI), mortality (MOR), number of health treatments (TRT), health scores (Hscore), carcass weight (CWT), back fat (CBF) and loin depth (CLD), dressing percentage (DRS), lean yield (LYLD), day-to-day variation in feed intake and duration (VARFI and VARDUR), and the proportion of off-feed days (OFFFI and OFFDUR). Analyses were by mixed linear models with genomic relationships. The resilience traits TRT, MOR, and Hscore were lowly heritable (up to 0.15) but had high genetic correlations with each other. Performance traits ADG, ADFI, ADFD, FCR, RFI, and carcass traits were moderate to highly heritable (0.17 to 0.49). Heritabilities of resilience indicator traits OFF and VAR had low to moderate heritabilities (0.08 to 0.23) but were higher when based on duration versus amount. ADFI had a low genetic correlation with ADFD (0.13). ADG in the challenge nursery had stronger negative genetic correlations with both TRT and MOR than ADG in the finisher (-0.37 to -0.74 versus -0.15 to -0.56). ADFI and FCR had moderate negative (-0.21 to -0.39) and positive (0.34 to 0.49), respectively, genetic correlations with TRT and MOR. ADFD and RFI had very low genetic correlations with TRT and MOR. CWT and DRS were moderately negatively correlated with TRT and MOR (-0.33 to -0.59). Resilience indicator traits based on feed intake or duration had moderate to high positive genetic correlations with TRT (0.18 to 0.81) and MOR (0.33 to 0.87). In conclusion, performance and resilience traits under a polymicrobial disease challenge are heritable and can be changed by selection. Phenotypes extracted from feed intake patterns can be used as genetic indicator traits for disease resilience. Most promising is day-to-day variation in intake duration, which had a sizeable heritability (0.23) and favorable genetic correlations with mortality (0.79) and treatment rate (0.20).
Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC). In the present study, increased DNMT3A expression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied that DNMT3A is involved in hepatocellular carcinogenesis. Depletion of DNMT3A in HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their 5′ region. 13 of them including PTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation of PTEN promoter was observed in DNMT3A-depleted cells implying that DNMT3A silenced PTEN via DNA methylation. These results provide insights into the mechanisms of DNMT3A to regulate TSGs by an epigenetic approach in HCC.
The modified-relative-dose-response (MRDR) test, which has been used extensively throughout the world for assessing vitamin A status, has been simplified. The major methodologic change resulting from the current studies in Indonesia is the use of graded standard doses of 3,4-didehydroretinyl acetate (DRA) based on the age range of the population of interest. Instead of a dose of 0.35 mumol/kg body wt, standard doses of 5.3 mumol for children younger than 6 y, 7.0 mumol for children between 6 and 12 y of age, and 8.8 mumol for adults and children > 12 y of age are suggested for field use. The acceptable time between administering the oral dose and obtaining a blood sample was validated as being 4-7 h in a group of children (n = 84) by taking two blood samples per child between 3 and 7 h after dosing with DRA. Furthermore, DRA in vitamin E-containing corn oil, with or without the addition of 4.6 mmol all-rac-alpha-tocopheryl acetate/L, was found to be stable for > or = 18 mo at 2 degrees C and at -20 degrees C, but not at 22 degrees C or at 37 degrees C. When DRA was stored in amber glass vials, stability was affected more by temperature than by exposure to room light. In keeping with earlier studies in adults, the ratio of 3,4-didehydro-retinol to retino tends to be independent of body weight. Indeed, slower growing children (ie, those with lower weight-for-age) may have a somewhat better vitamin A status than their heavier counterparts.
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