DNA methylation of amino acid transporter genes in the human placenta.

INTRODUCTION: Placental transfer of amino acids via amino acid transporters is essential for fetal growth. Little is known about the epigenetic regulation of amino acid transporters in placenta. This study investigates the DNA methylation status of amino acid transporters and their expression across gestation in human placenta. METHODS: BeWo cells were treated with 5-aza-2'-deoxycytidine to inhibit methylation and assess the effects on amino acid transporter gene expression. The DNA methylation levels of amino acid transporter genes in human placenta were determined across gestation using DNA methylation array data. Placental amino acid transporter gene expression across gestation was also analysed using data from publically available Gene Expression Omnibus data sets. The expression levels of these transporters at term were established using RNA sequencing data. RESULTS: Inhibition of DNA methylation in BeWo cells demonstrated that expression of specific amino acid transporters can be inversely associated with DNA methylation. Amino acid transporters expressed in term placenta generally showed low levels of promoter DNA methylation. Transporters with little or no expression in term placenta tended to be more highly methylated at gene promoter regions. The transporter genes SLC1A2, SLC1A3, SLC1A4, SLC7A5, SLC7A11 and SLC7A10 had significant changes in enhancer DNA methylation across gestation, as well as gene expression changes across gestation. CONCLUSION: This study implicates DNA methylation in the regulation of amino acid transporter gene expression. However, in human placenta, DNA methylation of these genes remains low across gestation and does not always play an obvious role in regulating gene expression, despite clear evidence for differential expression as gestation proceeds.

A review of mathematical models for the formation of vascular networks.

Two major mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former term describes the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter term describes the sprouting of new vessels from an existing capillary or post-capillary venule. Similar mechanisms are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis. A number of mathematical approaches have been used to analyze these phenomena. In this paper, we review the different types of models, with special emphasis on their ability to reproduce different biological systems and to predict measurable quantities which describe the overall processes. Finally, we highlight the advantages specific to each of the different modelling approaches.

Thermomechanical investigation of the cortical bone analogue in third-generation Sawbones femurs.

The mechanical properties of the short glass fibre reinforced (SGFR) epoxy resin used as the cortical bone analogue in the third-generation Sawbones femurs were investigated for use within orthopaedic benchtop tests. Tensile and four-point bending tests were used to assess the material properties of the SGFR epoxy at both room (22 'C) and body temperatures (37 degrees C). The 20 standardized specimens used for the materials testing were machined from third-generation Sawbones femurs. The flexural properties of the specimens were determined using ASTM D6272-02 and the tensile properties were obtained using ASTM D638-02. The mean (and standard deviation, or SD) values of the modulus of elasticity in four-point bending for room and body temperature specimens of 7.8 (0.64) GPa and 2.8 (0.66) GPa respectively were significantly different (P < 0.001). The mean (and SD) values of the modulus of elasticity in tension for the room and body temperature specimens of 9.4 (0.8) GPa and 5.4 (1.3) GPa respectively were also significantly different (P = 0.02). The modulus of elasticity of SGFR epoxy is highly temperature dependent. A reduction in the modulus of elasticity of up to 63 per cent was observed when increasing the temperature of the specimens from room to body temperature. SGFR epoxy Sawbones do not accurately represent the material properties of bone at body temperature.

Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice.

T lymphocytes and monocyte/macrophages are prominent components of atherosclerotic lesions, and many of these cells are activated and secreting cytokines. To determine the role of these cells in the pathogenesis of atherosclerosis, we studied its development in T-cell-deficient mice fed a high fat atherogenic diet. Depleting euthymic mice of their CD4+ lymphocytes by 20 weekly injections of CD4 monoclonal antibodies reduced the mean area of their aortic lesions by approximately 70%. Similarly, the mean lesion area of T-cell-deficient nude (nu/nu) mice was 10% of the size of that of their heterozygote (nu/+) litter mates. Flow cytometric studies of splenic T cells and analyses of serum total and HDL cholesterol of these mice indicated that the differences in mean lesion areas among the experimental groups were most closely correlated with differences in splenic T cells content. These studies suggest that in these two models T lymphocytes contribute to the pathogenesis of early atherosclerotic lesions and that a further understanding of this phenomenon may provide future approaches toward the prevention and treatment of the disease.