Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence.

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose

The Physicist's Guide to the Orchestra

An experimental study of strings, woodwinds (organ pipe, flute, clarinet, saxophone and recorder), and the voice was undertaken to illustrate the basic principles of sound production in music instruments. The setup used is simple and consists of common laboratory equipment. Although the canonical examples (standing wave on a string, in an open and closed pipe) are easily reproduced, they fail to explain the majority of the measurements. The reasons for these deviations are outlined and discussed.Comment: 11 pages, 10 figures (jpg files). Submitted to European Journal of Physic

Plant-Derived Polyphenols Modulate Human Dendritic Cell Metabolism and Immune Function via AMPK-Dependent Induction of Heme Oxygenase-1

Polyphenols are important immunonutrients which have been investigated in the context of inflammatory and autoimmune disease due to their significant immunosuppressive properties. However, the mechanism of action of many polyphenols is unclear, particularly in human immune cells. The emerging field of immunometabolism has highlighted the significance of metabolic function in the regulation of immune cell activity, yet the effects of polyphenols on immune cell metabolic signaling and function has not been explored. We have investigated the effects of two plant-derived polyphenols, carnosol and curcumin, on the metabolism of primary human dendritic cells (DC). We report that human DC display an increase in glycolysis and spare respiratory capacity in response to LPS stimulation, which was attenuated by both carnosol and curcumin treatment. The regulation of DC metabolism by these polyphenols appeared to be mediated by their activation of the cellular energy sensor, AMP-activated Protein Kinase (AMPK), which resulted in the inhibition of mTOR signaling in LPS-stimulated DC. Previously we have reported that both carnosol and curcumin can regulate the maturation and function of human DC through upregulation of the immunomodulatory enzyme, Heme Oxygenase-1 (HO-1). Here we also demonstrate that the induction of HO-1 by polyphenols in human DC is dependent on their activation of AMPK. Moreover, pharmacological inhibition of AMPK was found to reverse the observed reduction of DC maturation by carnosol and curcumin. This study therefore describes a novel relationship between metabolic signaling via AMPK and HO-1 induction by carnosol and curcumin in human DC, and characterizes the effects of these polyphenols on DC immunometabolism for the first time. These results expand our understanding of the mechanism of action of carnosol and curcumin in human immune cells, and suggest that polyphenol supplementation may be useful to regulate the metabolism and function of immune cells in inflammatory and metabolic disease

Superficial simplicity of the 2010 El Mayor–Cucapah earthquake of Baja California in Mexico

The geometry of faults is usually thought to be more complicated at the surface than at depth and to control the initiation, propagation and arrest of seismic ruptures. The fault system that runs from southern California into Mexico is a simple strike-slip boundary: the west side of California and Mexico moves northwards with respect to the east. However, the M_w 7.2 2010 El Mayor–Cucapah earthquake on this fault system produced a pattern of seismic waves that indicates a far more complex source than slip on a planar strike-slip fault. Here we use geodetic, remote-sensing and seismological data to reconstruct the fault geometry and history of slip during this earthquake. We find that the earthquake produced a straight 120-km-long fault trace that cut through the Cucapah mountain range and across the Colorado River delta. However, at depth, the fault is made up of two different segments connected by a small extensional fault. Both segments strike N130° E, but dip in opposite directions. The earthquake was initiated on the connecting extensional fault and 15 s later ruptured the two main segments with dominantly strike-slip motion. We show that complexities in the fault geometry at depth explain well the complex pattern of radiated seismic waves. We conclude that the location and detailed characteristics of the earthquake could not have been anticipated on the basis of observations of surface geology alone

Development of strategies for effective communication of food risks and benefits across Europe: Design and conceptual framework of the FoodRisC project

The FoodRisC project is funded under the Seventh Framework Programme (CORDIS FP7) of the European Commission; Grant agreement no.: 245124. Copyright @ 2011 Barnett et al.BACKGROUND: European consumers are faced with a myriad of food related risk and benefit information and it is regularly left up to the consumer to interpret these, often conflicting, pieces of information as a coherent message. This conflict is especially apparent in times of food crises and can have major public health implications. Scientific results and risk assessments cannot always be easily communicated into simple guidelines and advice that non-scientists like the public or the media can easily understand especially when there is conflicting, uncertain or complex information about a particular food or aspects thereof. The need for improved strategies and tools for communication about food risks and benefits is therefore paramount. The FoodRisC project ("Food Risk Communication - Perceptions and communication of food risks/benefits across Europe: development of effective communication strategies") aims to address this issue. The FoodRisC project will examine consumer perceptions and investigate how people acquire and use information in food domains in order to develop targeted strategies for food communication across Europe.METHODS/DESIGN: This project consists of 6 research work packages which, using qualitative and quantitative methodologies, are focused on development of a framework for investigating food risk/benefit issues across Europe, exploration of the role of new and traditional media in food communication and testing of the framework in order to develop evidence based communication strategies and tools. The main outcome of the FoodRisC project will be a toolkit to enable coherent communication of food risk/benefit messages in Europe. The toolkit will integrate theoretical models and new measurement paradigms as well as building on social marketing approaches around consumer segmentation. Use of the toolkit and guides will assist policy makers, food authorities and other end users in developing common approaches to communicating coherent messages to consumers in Europe.DISCUSSION: The FoodRisC project offers a unique approach to the investigation of food risk/benefit communication. The effective spread of food risk/benefit information will assist initiatives aimed at reducing the burden of food-related illness and disease, reducing the economic impact of food crises and ensuring that confidence in safe and nutritious food is fostered and maintained in Europe.This article is available through the Brunel Open Access Publishing Fund

The Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory

The Photodetector Array Camera and Spectrometer (PACS) is one of the three science instruments on ESA's far infrared and submillimetre observatory. It employs two Ge:Ga photoconductor arrays (stressed and unstressed) with 16x25 pixels, each, and two filled silicon bolometer arrays with 16x32 and 32x64 pixels, respectively, to perform integral-field spectroscopy and imaging photometry in the 60-210\mu\ m wavelength regime. In photometry mode, it simultaneously images two bands, 60-85\mu\ m or 85-125\mu\m and 125-210\mu\ m, over a field of view of ~1.75'x3.5', with close to Nyquist beam sampling in each band. In spectroscopy mode, it images a field of 47"x47", resolved into 5x5 pixels, with an instantaneous spectral coverage of ~1500km/s and a spectral resolution of ~175km/s. We summarise the design of the instrument, describe observing modes, calibration, and data analysis methods, and present our current assessment of the in-orbit performance of the instrument based on the Performance Verification tests. PACS is fully operational, and the achieved performance is close to or better than the pre-launch predictions

A New Stalked Filter-Feeder from the Middle Cambrian Burgess Shale, British Columbia, Canada

Burgess Shale-type deposits provide invaluable insights into the early evolution of body plans and the ecological structure of Cambrian communities, but a number of species, continue to defy phylogenetic interpretations. Here we extend this list to include a new soft-bodied animal, Siphusauctum gregarium n. gen. and n. sp., from the Tulip Beds (Campsite Cliff Shale Member, Burgess Shale Formation) of Mount Stephen (Yoho National Park, British Columbia). With 1,133 specimens collected, S. gregarium is clearly the most abundant animal from this locality

Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine

The selenocysteine insertion sequence (SECIS) element directs the translational recoding of UGA as selenocysteine. In eukaryotes, the SECIS is located downstream of the UGA codon in the 3′-UTR of the selenoprotein mRNA. Despite poor sequence conservation, all SECIS elements form a similar stem-loop structure containing a putative kink-turn motif. We functionally characterized the 26 SECIS elements encoded in the human genome. Surprisingly, the SECIS elements displayed a wide range of UGA recoding activities, spanning several 1000-fold in vivo and several 100-fold in vitro. The difference in activity between a representative strong and weak SECIS element was not explained by differential binding affinity of SECIS binding Protein 2, a limiting factor for selenocysteine incorporation. Using chimeric SECIS molecules, we identified the internal loop and helix 2, which flank the kink-turn motif, as critical determinants of UGA recoding activity. The simultaneous presence of a GC base pair in helix 2 and a U in the 5′-side of the internal loop was a statistically significant predictor of weak recoding activity. Thus, the SECIS contains intrinsic information that modulates selenocysteine incorporation efficiency

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio