Comparison of DNA methylation levels of repetitive loci during bovine development

<p> Abstract</p> <p>Background</p> <p>DNA methylation of cytosine residues in CpG dinucleotide controls gene expression and dramatically changes during development. Its pattern is disrupted in cloned animals suggesting incomplete reprogramming during somatic cell nuclear transfer (the first reprogramming). However, the second reprogramming occurs in the germ cells and epigenetic errors in somatic cells of cloned animals should be erased. To analyze the DNA methylation changes on the spermatogenesis of bulls, we measured DNA methylation levels of three repetitive elements in blastocysts, blood and sperm.</p> <p>Methods</p> <p>DNA from PBLs (peripheral blood leukocytes), sperm and individual IVF (<it>in vitro</it> fertilized) and parthenogenetic blastocysts was isolated and bisulfite converted. Three repetitive elements; Satellite I, Satellite II and <it>art2</it> sequences were amplified by PCR with specific pairs of primers. The PCR product was then cut by restriction enzymes and analyzed by agarose gel electrophoresis for determining the DNA methylation levels.</p> <p>Results</p> <p>Both Satellite I and Satellite II sequences were highly methylated in PBLs, whereas hypo-methylated in sperm and blastocysts. The <it>art2</it> sequence was half methylated both in PBLs and sperm but less methylated in blastocysts. There was no difference in DNA methylation levels between IVF and parthenogenetic blastocysts.</p> <p>Conclusions</p> <p>These results suggest that there is a dynamic change of DNA methylation during embryonic development and spermatogenesis in cattle. Satellite I and Satellite II regions are methylated during embryogenesis and then de-methylated during spermatogenesis. However, <it>art2</it> sequences are not de-methylated during spermatogenesis, suggesting that this region is not reprogrammed during germ cell development. These results show dynamic changes of DNA methylation levels during bovine embryogenesis, especially genome-wide reprogramming in germ cells.</p

A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats

Dopamine (DA) agonists are widely used as primary treatments for Parkinson's disease. However, they do not prevent progressive degeneration of dopaminergic neurons, the central pathology of the disease. In this study, we found that subcutaneous injection of a cytokine mixture containing granulocyte macrophage colony-stimulating factor and interleukin-3 (IL-3) markedly suppressed dopaminergic neurodegeneration in 6-hydroxydopamine-lesioned rats, an animal model of Parkinson's disease. The cytokine mixture suppressed the decrease of DA content in the striatum, and ameliorated motor function in the lesioned rats. In response to the cytokine injection, dopaminergic neurons in the substantia nigra pars compacta increased expression of the antiapoptotic protein Bcl-xL. Microglial activation in the pars compacta was evident in both the saline- and cytokine-injected rats. However, the cytokine mixture suppressed expression of the proinflammatory cytokines IL-1β and tumor necrosis factors α, and upregulated the neuroprotective factors insulin-like growth factor-1 and hepatocyte growth factor. Similar responses were observed in cultured microglia. Detailed morphometric analyses revealed that NG2 proteoglycan-expressing glial cells increased in the cytokine-injected rats, while astrocytic activation with increased expression of antioxidative factors was evident only in the saline-injected rats. Thus, the present findings show that the cytokine mixture was markedly effective in suppressing neurodegeneration. Its neuroprotective effects may be mediated by increased expression of Bcl-xL in dopaminergic neurons, and the activation of beneficial actions of microglia that promote neuronal survival. Furthermore, this cytokine mixture may have indirect actions on NG2 proteoglycan-expressing glia, whose role may be implicated in neuronal survival

Whole brain Probabilistic Generative Model toward Realizing Cognitive Architecture for Developmental Robots

Building a humanlike integrative artificial cognitive system, that is, an artificial general intelligence, is one of the goals in artificial intelligence and developmental robotics. Furthermore, a computational model that enables an artificial cognitive system to achieve cognitive development will be an excellent reference for brain and cognitive science. This paper describes the development of a cognitive architecture using probabilistic generative models (PGMs) to fully mirror the human cognitive system. The integrative model is called a whole-brain PGM (WB-PGM). It is both brain-inspired and PGMbased. In this paper, the process of building the WB-PGM and learning from the human brain to build cognitive architectures is described.Comment: 55 pages, 8 figures, submitted to Neural Network

Association between Oral Health Status and Diabetic Nephropathy-Related Indices in Japanese Middle-Aged Men

Oral health status is known to be associated with lifestyle-related diseases such as diabetes and chronic kidney disease. In Japan, around 40% of hemodialysis cases are patients with diabetic nephropathy. The aim of this study was to clarify the association between oral health status and diabetic nephropathy-related indices in Japanese middle-aged men. Sixty-six men (age range: 55–64 years) with ≥20 remaining teeth and who received public medical checkups and oral examinations were enrolled. We examined correlations of age, body mass index, HbA1c, HDL-C, LDL-C, neutral fat, serum creatinine, and the estimated glomerular filtration rate (eGFR) with the number of remaining teeth or the community periodontal index (CPI) score (periodontal pocket < 4mm: 0, 4–6 mm: 1, ≥6 mm: 2). A positive correlation between the CPI score and serum creatinine and a negative correlation between CPI score and eGFR (Spearman’s rank correlation coefficient, r = 0.459, p < 0.01, and r = −0.460, p < 0.01, respectively) were observed. The mean eGFR in the CPI score 0 group was significantly higher than that in the CPI score 1/2 group (82.6 vs. 70.7, Student’s t-test, p < 0.01). Logistic regression analysis using eGFR as a dependent variable and age, CPI score, body mass index, HbA1c, and neutral fat as independent variables suggested that low eGFR (<60) could be attributed to CPI score (OR = 3.169, 95% CI: 1.031–9.742, p = 0.044). These results suggest a possible association between periodontal status and renal function in Japanese middle-aged men. Periodontal condition is controlled by oral prophylaxis, and periodontal disease and chronic kidney disease have some common risk factors. Thus, periodontal management can contribute to the prevention of severe chronic kidney disease