Maternal nutritional status, C1 metabolism and offspring DNA methylation: a review of current evidence in human subjects.

: Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn2+ is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl2), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn2+ delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl2 dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25–50 mg/kg/day MnCl2 via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl2 dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl2 via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl2 to use for different study designs

Branching dendrites with resonant membrane: a “sum-over-trips” approach

Dendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the “sum-over-trips” approach (Abbott et al. in Biol Cybernetics 66, 49–60 1991). To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an Ih current contributes to a voltage overshoot at the soma

Newtonian flow inside carbon nanotube with permeable boundary taking into account van der Waals forces

Here, water flow inside large radii semi-infinite carbon nanotubes is investigated. Permeable wall taking into account the molecular interactions between water and a nanotube, and the slip boundary condition will be considered. Furthermore, interactions among molecules are approximated by the continuum approximation. Incompressible and Newtonian fluid is assumed, and the Navier-Stokes equations, after certain assumptions, transformations and derivations, can be reduced into two first integral equations. In conjunction with the asymptotic expansion technique, we are able to derive the radial and axial velocities analytically, capturing the effect of the water leakage, where both mild and exceptionally large leakages will be considered. The radial velocity obeys the prescribed boundary condition at the (im)permeable wall. Through the mean of the radial forces, the sufficiently large leakages will enhance the radial velocity at the center of the tube. On the other hand, unlike the classical laminar flow, the axial velocity attains its maximum at the wall due to the coupling effect with the radial forces as water is being pushed into the proximity of the inner wall. In addition, the axial velocity and the flux with the consideration of the suck-in forces, induced by the tubes’ entry turn out to be one order higher than that without the suck-in forces. All the aforementioned considerations might partially resolve the mysteriously high water penetration through nanotubes. Axial velocity also drops with the tube’s length when the water leakage is permitted and the suck-in forces will ease the decline rate of the axial velocity. The present mathematical framework can be directly employed into the water flow inside other porous nano-materials, where large water leakage is permitted and therefore are of huge practical impact on ultra-filtration and environmental protection

Interstellar scintillation as the origin of rapid radio variability in the quasar J1819+3845

Quasars shine brightly due to the liberation of gravitational energy as matter falls onto a supermassive black hole in the centre of a galaxy. Variations in the radiation received from active galactic nuclei (AGN) are studied at all wavelengths, revealing the tiny dimensions of the region and the processes of fuelling the black hole. Some AGN are variable at optical and shorter wavelengths, and display radio outbursts over years and decades. These AGN often also show faster variations at radio wavelengths (intraday variability, IDV) which have been the subject of much debate. The simplest explanation, supported by a correlation in some sources between the optical (intrinsic) and faster radio variations, is that the rapid radio variations are intrinsic. However, this explanation implies physically difficult brightness temperatures, suggesting that the variations may be due to scattering of the incident radiation in the interstellar medium of our Galaxy. Here we present results which show unambiguously that the variations in one extreme case are due to interstellar scintillation. We also measure the transverse velocity of the scattering material, revealing a surprising high velocity plasma close to the Solar System

Stereoselective handling of perhexiline:Implications regarding accumulation within the human myocardium

Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (−) perhexiline may selectively modulate heart rate reduction

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis

Background Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth. Results It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms. Conclusion Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans

Temporal patterns in habitat use by small cetaceans at an oceanographically dynamic marine renewable energy test site in the Celtic Sea

Shelf-seas are highly dynamic and oceanographically complex environments, which likely influences the spatio-temporal distributions of marine megafauna such as marine mammals. As such, understanding natural patterns in habitat use by these animals is essential when attempting to ascertain and assess the impacts of anthropogenically induced disturbances, such as those associated with marine renewable energy installations (MREIs). This study uses a five year (2009–2013) passive acoustics (C-POD) dataset to examine the use of an oceanographically dynamic marine renewable energy test site by small cetaceans, dolphins (unspecified delphinids) and harbour porpoises Phocoena phocoena, in the southern Celtic Sea. To examine how temporal patterns in habitat use across the site related to oceanographic changes occurring over broad seasonal scales as well as those driven by fine scale (bi-weekly) localised processes (that may be masked by seasonal trends), separate analyses were conducted using (1) all daily animal detection rates spanning the entire five year dataset and (2) daily animal detection rates taken only during the summer months (defined as mid-June to mid-October) of 2010 (when continuous monitoring was carried out at multiple discrete locations across the site). In both instances, generalised additive mixed effects models (GAMMs) were used to link detection rates to a suite of environmental variables representative of the oceanography of the region. We show that increased harbour porpoise detection rates in the late winter/early spring (January–March) are associated with low sea surface temperatures (SST), whilst peaks in dolphin detection rates in the summer (July–September) coincide with increased SSTs and the presence of a tidal-mixing front. Moreover, across the summer months of 2010, dolphin detection rates were found to respond to small scale changes in SST and position in the spring-neap cycle, possibly reflective of a preference for the stratified waters immediately offshore of the front. Together, these findings suggest that habitat use by small cetaceans within shelf-seas is temporally variable, species specific and likely driven by complex bottom-up processes. As such, the effective conservation management of shelf-seas requires that we understand the dynamic complexities of these systems and the species that inhabit them. In particular, we emphasise the need for a good understanding of the natural drivers of habitat use by marine megafauna before the potential impacts of anthropogenically induced disturbances, such as those associated with the construction, maintenance and operation of MREIs, can be assessed