What are interesterified fats and should we be worried about them in our diet?

Interesterified (IE) fats are used in a wide range of food products and were introduced as a replacement for trans fats, which are known to be detrimental to cardiovascular health. However, the effects of interesterification on metabolism and subsequent effects on cardiovascular health are not understood and previous studies have seldom investigated industrially-relevant IE fats. No legislation currently exists regarding the labelling of IE fats in food products and therefore estimates of average consumption rates in the UK population are currently unavailable. In order to meet the urgent need for a systematic investigation of the health effects of consumer-relevant IE fats, it is essential to estimate current IE fat intakes and to investigate biological mechanisms that might mediate acute and chronic cardiometabolic effects of commercially relevant IE fats.

Evidence for the transmission of neoplastic properties from transformed to normal human stem cells.

The in vivo relationship between human tumor cells and interacting normal cells in their local environment is poorly understood. Here, using a uniquely developed in vitro co-culture system for human embryonic stem cells (hESCs), we examined the interactions between transformed and normal human stem cells. Co-culture of transformed-hESCs (t-hESCs) with normal hESCs led to enhanced self-renewal and niche independence in normal hESCs. Global gene expression analysis of normal hESCs after timed exposure to t-hESCs indicated a transition of the molecular network controlling the hESC state, which included epigenetic changes, towards neoplastic features. These included enhanced pluripotent marker expression and a differentiation blockade as major hallmark changes. Functional studies revealed a loss in normal terminal differentiation programs for both hematopoiesis and neural lineages after normal stem cell co-culture with transformed variants. This transmission of neoplastic properties from t-hESCs to normal hESCs was dependent on direct cell-cell contact. Our study indicates that normal human stem cells can co-opt neoplastic cancer stem cell properties, raising the possibility that assimilation of healthy cells towards neoplastic behavior maybe a contributing feature of sustained tumorigenesis in vivo.

Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science - Addressing the ODWAC New Recommendation.

Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from tritium exposure at 20 Bq/L would be orders of magnitude less than that from exposure to natural background sources of radiation. The new proposed standard would set the radiation dose limit for drinking water to 0.0003 mSv/year, which is equivalent to approximately three times the dose from naturally occurring tritium in drinking water. This new standard is incongruent with national and international standards for safe levels of radiation exposure, currently set at 1 mSv/year for the general public. Scientific research from leading authorities on the carcinogenic health effects of tritium exposure supports the notion that the current standard of 7,000 Bq/L (annual dose of 0.1 mSv) is a safe standard for human health.Policy-making for the purpose of regulating tritium levels in drinking water is a dynamic multi-stage process that is influenced by more than science alone. Ethics, economics, and public perception also play important roles in policy development; however, these factors sometimes undermine the scientific evidence that should form the basis of informed decision making. Consequently, implementing a new standard without a scientific basis may lead the public to perceive that risks from tritium have been historically underestimated. It was concluded that the new recommendation is not supported by any new scientific insight regarding negative consequences of low dose effects, and may be contrary to new data on the potential benefits of low dose effects. Given the lack of cost versus benefit analysis, this type of dramatic policy change could have detrimental effects to society from an ethical, economical, and public perception perspective.

Modified rare earth semiconductor oxide as a new nucleotide probe.

Recent rapid developments in biological analysis, medical diagnosis, pharmaceutical industry, and environmental control fuel the urgent need for recognition of particular DNA sequences from samples. Currently, DNA detection techniques use radiochemical, enzymatic, fluorescent, or electrochemiluminescent methods; however, these techniques require costly labeled DNA and highly skilled and cumbersome procedure, which prohibit any in-situ monitoring. Here, we report that hybridization of surface-immobilized single-stranded oligonucleotide on praseodymium oxide (evaluated as a biosensor surface for the first time) with complimentary strands in solution provokes a significant shift of electrical impedance curve. This shift is attributed to a change in electrical characteristics through modification of surface charge of the underlying modified praseodymium oxide upon hybridization with the complementary oligonucelotide strand. On the other hand, using a noncomplementary single strand in solution does not create an equivalent change in the impedance value. This result clearly suggests that a new and simple electrochemical technique based on the change in electrical properties of the modified praseodymium oxide semiconductor surface upon recognition and transduction of a biological event without using labeled species is revealed.

Escherichia coli flavohaemoglobin (Hmp) with equistoichiometric FAD and haem contents has a low affinity for dioxygen in the absence or presence of nitric oxide.

A purification procedure for flavohaemoglobin Hmp (NO oxygenase) is described that gives high yields of protein with equistoichiometric haem and FAD contents. H(2)O(2) accumulated on NADH oxidation by the purified protein and in cell extracts with elevated Hmp contents. H(2)O(2) probably arose by dismutation from superoxide, which was also detectable during oxygen reduction; water was not a product. In the absence of agents that scavenge superoxide and peroxide, the mean K(m) for oxygen was 80 microM; the addition of 15 microM FAD decreased the K(m) for oxygen to 15 microM without a change in V(max) but catalysed cyanide-insensitive oxygen consumption, attributed to electron transfer from flavins to O(2). Purified Hmp consumed NO in the absence of added FAD (approx. 1 O(2) per NO), which is consistent with NO oxygenation. However, half-maximal rates of NO-stimulated O(2) consumption required approx. 47 microM O(2); NO removal was ineffective at physiologically relevant O(2) concentrations (below approx. 30 microM O(2)). On exhaustion of O(2), NO was removed by a cyanide-sensitive process attributed to NO reduction, with a turnover number approx. 1% of that for oxygenase activity. These results suggest that the ability of Hmp to detoxify NO might be compromised in hypoxic environments.

Flavohemoglobin, a globin with a peroxidase-like catalytic site.

Biochemical studies of flavohemoglobin (Hmp) from Escherichia coli suggest that instead of aerobic oxygen delivery, a dioxygenase converts NO to NO3(-) and anaerobically, an NO reductase converts NO to N(2)O. To investigate the structural features underlying the chemical reactivity of Hmp, we have measured the resonance Raman spectra of the ligand-free ferric and ferrous protein and the CO derivatives of the ferrous protein. At neutral pH, the ferric protein has a five-coordinate high-spin heme, similar to peroxidases. In the ferrous protein, a strong iron-histidine stretching mode is present at 244 cm(-1). This frequency is much higher than that of any other globin discovered to date, although it is comparable to those of peroxidases, suggesting that the proximal histidine has imidazolate character. In the CO derivative, an open and a closed conformation were detected. The distal environment of the closed conformation is very polar, where the heme-bound CO strongly interacts with the B10 Tyr and/or the E7 Gln. These data demonstrate that the active site structure of Hmp is very similar to that of peroxidases and is tailored to perform oxygen chemistry.

Flavohemoglobin Hmp affords inducible protection for Escherichia coli respiration, catalyzed by cytochromes bo' or bd, from nitric oxide.

Respiration of Escherichia coli catalyzed either by cytochrome bo' or bd is sensitive to micromolar extracellular NO; extensive, transient inhibition of respiration increases as dissolved oxygen tension in the medium decreases. At low oxygen concentrations (25-33 microm), the duration of inhibition of respiration by 9 microm NO is increased by mutation of either oxidase. Respiration of an hmp mutant defective in flavohemoglobin (Hmp) synthesis is extremely NO-sensitive (I(50) about 0.8 microm); conversely, cells pre-grown with sodium nitroprusside or overexpressing plasmid-borne hmp(+) are insensitive to 60 microm NO and have elevated levels of immunologically detectable Hmp. Purified Hmp consumes O(2) at a rate that is instantaneously and extensively (>10-fold) stimulated by NO due to NO oxygenase activity but, in the absence of NO, Hmp does not contribute measurably to cell oxygen consumption. Cyanide binds to Hmp (K(d) 3 microm). Concentrations of KCN (100 microm) that do not significantly inhibit cell respiration markedly suppress the protection of respiration from NO afforded by Hmp and abolish NO oxygenase activity of purified Hmp. The results demonstrate the role of Hmp in protecting respiration from NO stress and are discussed in relation to the energy metabolism of E. coli in natural O(2)-depleted environments.

Giant Axons and Escape Swimming in Euplokamis dunlapae (Ctenophora: Cydippida).

Euplokamis dunlapae responds to anterior stimulation by reversing the beat direction of its comb plate cilia and swimming rapidly backwards. It responds to posterior stimulation by swimming forwards at an accelerated rate. Video playback and laser monitoring were used to analyze changes in the pattern of ciliary beating, while electrical activity was recorded extracellularly. Escape responses occur with latencies of less than 150 ms and involve greatly increased ciliary beat frequencies. Giant axons run longitudinally along each of the eight comb rows, as shown by optical and electron microscopy. They form chains of overlapping neurons, with diameters of about 12 µm in life, and conducting at over 50 cm · s-1 as recorded with an extracellular electrode placed directly over the chain. The giant neurons are synaptically linked with smaller neurites of the general ectodermal nerve plexus, with each other, and with the ciliated cells of the comb plates. They appear to constitute a single system mediating rapid conduction of signals in either direction, but a full analysis was not attempted for lack of sufficient material. Electro-physiological examination of two other ctenophores (Pleurobrachia and Beroe) gives no indication of rapid conduction pathways, and these forms probably lack giant axons.

Novel cnidocysts of narcomedusae and a medusivorous ctenophore, and confirmation of kleptocnidism.

Cnidocysts have been examined from the tentacles of the ctenophore Haeckelia rubra (Euchlora rubra) and five species of hydrozoan narcomedusae (Solmundella bitentaculata, Aegina citrea, Solmissus marshalli, Solmissus albescens, and Cunina sp.) using TEM, both in sections and by firing whole cnidocysts onto EM grids. The study revealed that these apotrichous isorhiza cnidocysts have a novel morphology in which the intracapsular inverted tubule has five circumferential pleats when viewed in transverse section, rather than the usual three pleats. Accordingly, the definition of helicoptychoneme cnidocysts has been broadened to include both the usual three-pleated cnidocysts and these new five-pleated cnidocysts. In general, apotrichous isorhizas have subspherical capsules with a thick, bilayered wall, whose interior is nearly filled with the regularly coiled, helically folded, five-pleated inverted tubule. Upon discharge, the everted tubule is several mm long and the five circumferential pleats become manifested as five helical rows of spines running up the tubule, which has three morphologically different segments. The very short basal segment is devoid of ornamentation; the remaining proximal portion is characterized by five spirals of uniform, closely packed short spines; the long distal portion is characterized by a single spiral of regularly spaced large spines that derive from all five spirals-the five spirals are otherwise demarcated in the distal portion by 'scales' that are visible only with the electron microscope.