Background: Insulin-like growth factor 2 (IGF2) is a protein hormone known to regulate cell proliferation, growth, migration, differentiation and survival. The gene is parentally imprinted in the sense that transcripts are almost exclusively derived from the paternal allele. Loss of imprinting of the IGF2 gene is a recurrent observation in growth disorders that combine overgrowth with a variety of malignant tumours. Moreover, IGF2 has been proposed to play a role in the development of a variety of seemingly unrelated cancers that play an important role in geriatric medicine, e.g. breast cancer, colon cancer and lung cancer. Finally, IGF2 has been implicated in cardiovascular disease, since, for example, IGF2 has been shown to influence the size of atherosclerotic lesions. Objective: To summarize current knowledge about IGF2, its interactions with binding proteins and receptors and connections with key diseases. Methods: The contents of this paper were based on reviews of existing literature within the field. Results: There is a substantial amount of research linking IGF2 to growth disorders, cancer and to a much lesser degree cardiovascular disease. Some of the studies on IGF2 and tumour growth have yielded conflicting results, for instance regarding its effect on apoptosis. Conclusion: Today, our knowledge on how IGF2 is composed and interacts with receptors has come a long way. However, there is comparatively little information on how IGF2 affects tumour growth and cardiovascular diseases such as atherosclerosis. Thus, further research will be needed to elucidate the impact of IGF2 on key diseases.
Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals; they are expressed unevenly from the two parental alleles. Igf2 is a growth factor expressed in most normal tissues, solely from the paternal allele. H19 gene is transcribed (but not translated to a protein) from the maternal allele. Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both foetal and placental growth and also nutrient transfer from mother to offspring via the placenta. This article reviews epigenetic regulation of the Igf2/H19 gene-cluster that leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and three-dimensional partitioning of DNA in the nucleus. It is emphasized that key genomic features are conserved among mammals and have been functionally tested in mouse. 'The enhancer competition model', 'the boundary model' and 'the chromatin-loop model' are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways are discussed that can account for allelic methylation differences; there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of differential methylation pattern.
BackgroundIntensification of livestock production seen in many low- and middle-income countries is often believed to be associated with increased use of antimicrobials, and may hence contribute to the emergence of antimicrobial resistance. The aim of this study was to map antimicrobial use on small- (n = 25) and medium-scale (n = 27) pig farms in north-eastern Thailand, and to compare antimicrobial susceptibility of commensal Escherichia coli isolated from sows on these farms.MethodsInformation regarding pig husbandry and antimicrobial treatment regimens was obtained by the use of semi-structured questionnaires. Faecal samples were collected from three healthy sows at each farm, and Escherichia coli was cultured and analysed for antimicrobial susceptibility using the broth microdilution method. Multilevel regression models were used to compare antimicrobial susceptibility between isolates from small- and medium-scale farms.ResultsAll farms included in the study administered antimicrobials to their sows. Small-scale farmers most commonly (64%) decided themselves when to give antimicrobials and the majority (60%) bought the medicines at the local store or pharmacy, whereas farmers on medium-scale farms always discussed antimicrobial treatment with a veterinarian. Medium-scale farms used a greater diversity of antimicrobials than small-scale farms and did also administer antimicrobials in feed to a higher extent. High levels of antimicrobial resistance to several critically important antimicrobials for human medicine (including ciprofloxacin, streptomycin and ampicillin) were found in isolates from both small- and medium-scale farms. Resistance levels were significantly (P < 0.05) higher in isolates from medium-scale farms for several of the antimicrobials tested, as well as the level of multidrug-resistance (P = 0.026).ConclusionThe routines regarding access and administration of antimicrobials differed between the small- and medium-scale farms. Although the level of antimicrobial resistance, as well as multidrug-resistance, was higher in isolates from medium-scale farms, it cannot be concluded if this increase is a consequence of a more abundant use of antimicrobials, or a result of differences in administration routines.
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