Effect of maternal and post-weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult apc +/min and wild type mice

Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g., DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC) pathogenesis, we hypothesized low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine of wild type (WT) and Apc(+/Min) mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57Bl6/J mice were fed low or normal folate diets from mating with Apc(+/Min) males to the end of lactation. A sub-set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in four treatment groups of Apc(+/Min) and WT mice. p53 was more methylated in weaning and adult WT compared with Apc(+/Min) mice (p > 0.001). Igf2 and Apc were hypermethylated in adult Apc(+/Min) compared with WT mice (p = 0.004 and 0.012 respectively). Low maternal folate reduced p53 methylation in adults (p = 0.04). Low post-weaning folate increased Apc methylation in Apc(+/Min) mice only (p = 0.008 for interaction). These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene-specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc(+/Min) mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalized nutrition

Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1

Increased smooth muscle mass due to hyperplasia and hypertrophy of airway smooth muscle (ASM) cells is a common feature in asthma. Angiotensin II (Ang II), a potent vasoconstrictor and mitogen for a wide variety of cells, has recently been implicated in bronchoconstriction in asthmatics. However, a possible mitogenic role as well as underlying molecular mechanisms of this octapeptide in human ASM cells are not yet known. We studied the effects of Ang II on ASM cell proliferation and growth and on the expression of three transcription factors, egr-1, c-fos, and c-jun, as well as a cytokine, transforming growth factor-beta1 (TGF-beta1). Human ASM cells were isolated by enzymatic digestion of bronchial smooth muscle obtained from lung resection tissue. Confluent cells were growth-arrested and subsequently incubated with Ang II (100 nM) for different time periods and processed for the measurement of cell growth and gene expression. Ang II significantly induced DNA and protein synthesis in human ASM cells at 8 h, resulting in a net increase in the accumulation of protein over DNA (i.e., cellular hypertrophy) at 16 h of incubation. Cell counts and MTT-reduction assay, however, showed no increase in cell number as a result of Ang II stimulation. Ang II stimulated the expression of egr-1 and c-fos as early as 15 min, reaching maximum levels at 45 min, whereas the expression of c-jun peaked at 2 h of Ang II exposure. Furthermore, steady-state mRNA levels of TGF-beta1 were upregulated by Ang II after 4 h and reached peak levels at 16 h of incubation. Secretion of biologically active TGF-beta1 from human ASM cells was significantly (P <= 0.02) enhanced by Ang II incubation after 8 h, which remained elevated until 24 h. Our results suggest that the Ang II-induced transient early expression of transcription factors may regulate autocrine genes like TGF-beta1, of which the subsequent late upregulation could contribute to cellular hypertrophy during, for example, airway remodeling in asthma

Characterization of the Si/SiO2 interface morphology from quantum oscillations in Fowler–Nordheim tunneling currents

As design rules shrink to conform with ULSI device dimensions, gate dielectrics for MOSFET structures are required to be scaled to below ~60A where some properties of the device, such as interface roughness, that are negligible for thicker films become critical. Microroughness at the interface of ultrathin MOS capacitors has been shown to degrade these devices. The present study focuses on the interfacial region of -50A. SiO, on Si, using the quantum oscillations in Fowler-Nordheim tunneling currents as a probe. The oscillations are sensitive to the electron potential and abruptness of the film and interfaces. In particular, inelastic scattering and/or thickness inhomogeneities in the film will reduce the amplitude of the oscillations. We are using the amplitude of the oscillations to examine the degree of microroughness at the interface that results from a pre-oxidation high temperature anneal in an inert ambient containing various amounts of H20. AFM imaging has shown correlations supporting a microroughness induced change in the quantum oscillation amplitudes

A log analysis study of 10 years of ebook consumption in academic library collections

Even though libraries have been offering eBooks for more than a decade, very little is known about eBook access and consumption in academic library collections. This paper addresses this gap with a log analysis study of eBook access at the library of the University of Waikato. This in-depth analysis covers a period spanning 10 years of eBook use at this university. We draw conclusions about the use of eBooks at this institution and compare the results with other published studies of eBook usage at tertiary institutes

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)-alpha, a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF-alpha in a concentration- and time-dependent manner. TNF-alpha stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell-conditioned medium after 2 h of TNF-alpha stimulation. Protein levels increased in a time- and concentration-dependent manner. Release of IL-6 elicited by TNF-alpha was significantly inhibited by dexamethasone, cycloheximide, and nordihydroguaiaretic acid (NDGA). TNF-alpha did not alter DNA biosynthesis up to 48 h or cell numbers up to 120 h. Northern blot analysis of proto-oncogene expression revealed that c-fos and c-jun mRNA levels were elevated after 30 min of TNF-alpha incubation with maximum levels at 1 h and 45 min, respectively. Expression of c-fos mRNA was downregulated by NDGA. Four hours of TNF-alpha treatment resulted in translocation of c-jun immunofluorescence from the cytoplasm to the nucleus in human ASM cells. Our results suggest that despite the lack of a mitogenic response to TNF-alpha, upregulation of primary response genes in human ASM cells may account for the induction of proinflammatory cytokines, such as IL-6, in human airways

Study of heterogeneous nucleation of eutectic Si in high-purity Al-Si alloys with Sr addition

The official published version can be accessed from the link below - Copyright @ 2010 The Minerals, Metals & Materials Society and ASM InternationalAl-5 wt pct Si master-alloys with controlled Sr and/or P addition/s were produced using super purity Al 99.99 wt pct and Si 99.999 wt pct materials in an arc melter. The master-alloy was melt-spun resulting in the production of thin ribbons. The Al matrix of the ribbons contained entrained Al-Si eutectic droplets that were subsequently investigated. Differential scanning calorimetry, thermodynamic calculations, and transmission electron microscopy techniques were employed to examine the effect of the Sr and P additions on eutectic undercoolings and nucleation phenomenon. Results indicate that, unlike P, Sr does not promote nucleation. Increasing Sr additions depressed the eutectic nucleation temperature. This may be a result of the formation of a Sr phase that could consume or detrimentally affect potent AlP nucleation sites.This work is financially supported by the Higher Education Commission of Pakistan and managerially supported from the OAD

Habitable Zones of Host Stars During the Post-MS Phase

A star will become brighter and brighter with stellar evolution, and the distance of its habitable zone will become farther and farther. Some planets outside the habitable zone of a host star during the main sequence phase may enter the habitable zone of the host star during other evolutionary phases. A terrestrial planet within the habitable zone of its host star is generally thought to be suited to life existence. Furthermore, a rocky moon around a giant planet may be also suited to life survive, provided that the planet-moon system is within the habitable zone of its host star. Using Eggleton's code and the boundary flux of habitable zone, we calculate the habitable zone of our Solar after the main sequence phase. It is found that Mars' orbit and Jupiter's orbit will enter the habitable zone of Solar during the subgiant branch phase and the red giant branch phase, respectively. And the orbit of Saturn will enter the habitable zone of Solar during the He-burning phase for about 137 million years. Life is unlikely at any time on Saturn, as it is a giant gaseous planet. However, Titan, the rocky moon of Saturn, may be suitable for biological evolution and become another Earth during that time. For low-mass stars, there are similar habitable zones during the He-burning phase as our Solar, because there are similar core masses and luminosities for these stars during that phase.Comment: 6 pages, 7 figures. Accepted by Ap & S

Solution of coupled vertex and propagator Dyson-Schwinger equations in the scalar Munczek-Nemirovsky model

In a scalar $\phi^2\chi$ model, we exactly solve the vertex and $\phi$ propagator Dyson-Schwinger equations under the assumption of a spatially constant (Munczek-Nemirovsky) propagator for the $\chi$ field. Various truncation schemes are also considered.Comment: 7 pages,4 figures, minor changes, reference added for published versio

Using the inertia of spacecraft during landing to penetrate regoliths of the Solar System

The high inertia, i.e. high mass and low speed, of a landing spacecraft has the potential to drive a penetrometer into the subsurface without the need for a dedicated deployment mechanism, e.g., during Huygens landing on Titan. Such a method could complement focused subsurface exploration missions, particularly in the low gravity environments of comets and asteroids, as it is conducive to conducting surveys and to the deployment of sensor networks. We make full-scale laboratory simulations of a landing spacecraft with a penetrometer attached to its base plate. The tip design is based on that used in terrestrial Cone Penetration Testing (CPT) with a large enough shaft diameter to house instruments for analysing pristine subsurface material. Penetrometer measurements are made in a variety of regolith analogue materials and target compaction states. For comparison a copy of the ACC-E penetrometer from the Huygens mission to Titan is used. A test rig at the Open University is used and is operated over a range of speeds from 0.9 to 3 m s−1 and under two gravitational accelerations. The penetrometer was found to be sensitive to the target’s compaction state with a high degree of repeatability. The penetrometer measurements also produced unique pressure profile shapes for each material. Measurements in limestone powder produced an exponential increase in pressure with depth possibly due to increasing compaction with depth. Measurements in sand produced an almost linear increase in pressure with depth. Iron powder produced significantly higher pressures than sand presumably due to the rough surface of the grains increasing the grain-grain friction. Impacts into foamglas produced with both ACC-E and the large penetrometer produced an initial increase in pressure followed by a leveling off as expected in a consolidated material. Measurements in sand suggest that the pressure on the tip is not significantly dependent on speed over the range tested, which suggests bearing strength equations could be applied to impact penetrometry in sand-like regoliths. In terms of performance we find the inertia of a landing spacecraft, with a mass of 100 kg, is adequate to penetrate regoliths expected on the surface of Solar System bodies. Limestone powder, an analogue for a dusty surface, offered very little resistance allowing full penetration of the target container. Both iron powder, representing a stronger coarse grained regolith, and foamglas, representing a consolidated comet crust, could be penetrated to similar depths of around two to three tip diameters. Speed tests suggest a linear dependence of penetration depth on impact speed