Changes in the gut microbiota of mice orally exposed to methylimidazolium ionic liquids

Ionic liquids are salts used in a variety of industrial processes, and being relatively non-volatile, are proposed as environmentally-friendly replacements for existing volatile liquids. Methylimidazolium ionic liquids resist complete degradation in the environment, likely because the imidazolium moiety does not exist naturally in biological systems. However, there is limited data available regarding their mammalian effects in vivo. This study aimed to examine the effects of exposing mice separately to 2 different methylimidazolium ionic liquids (BMI and M8OI) through their addition to drinking water. Potential effects on key target organs-the liver and kidney-were examined, as well as the gut microbiome. Adult male mice were exposed to drinking water containing ionic liquids at a concentration of 440 mg/L for 18 weeks prior to examination of tissues, serum, urine and the gut microbiome. Histopathology was performed on tissues and clinical chemistry on serum for biomarkers of hepatic and renal injury. Bacterial DNA was isolated from the gut contents and subjected to targeted 16S rRNA sequencing. Mild hepatic and renal effects were limited to glycogen depletion and mild degenerative changes respectively. No hepatic or renal adverse effects were observed. In contrast, ionic liquid exposure altered gut microbial composition but not overall alpha diversity. Proportional abundance of Lachnospiraceae, Clostridia and Coriobacteriaceae spp. were significantly greater in ionic liquid-exposed mice, as were predicted KEGG functional pathways associated with xenobiotic and amino acid metabolism. Exposure to ionic liquids via drinking water therefore resulted in marked changes in the gut microbiome in mice prior to any overt pathological effects in target organs. Ionic liquids may be an emerging risk to health through their potential effects on the gut microbiome, which is implicated in the causes and/or severity of an array of chronic disease in humans

Using ultraviolet absorption spectroscopy to study nanoswitches based on non-canonical DNA structures

Non-canonical forms of DNA are attracting increasing interest for applications in nanotechnology. It is frequently convenient to characterize DNA molecules using a label-free approach such as ultraviolet absorption spectroscopy. In this paper we present the results of our investigation into the use of this technique to probe the folding of quadruplex and triplex nanoswitches. We confirmed that four G-quartets were necessary for folding at sub-mM concentrations of potassium and found that the wrong choice of sequence for the linker between G-tracts could dramatically disrupt folding, presumably due to the presence of kinetic traps in the folding landscape. In the case of the triplex nanoswitch we examined, we found that the UV spectrum showed a small change in absorbance when a triplex was formed. We anticipate that our results will be of interest to researchers seeking to design DNA nanoswitches based on quadruplexes and triplexes

Evaluation of Bug Club: a randomised control trial of a whole school primary aged reading programme

Literacy levels for children leaving primary school, internationally, remain a cause for concern. There is a limited evidence base for whole school reading programmes and resources in the first two years of primary school compared to studies of interventions for children with reading difficulties. This study used a longitudinal randomised control trial (RCT) design to evaluate the efficacy of Bug Club; a whole school reading programme. Data from1273 pupils in Years 1 and 2 from 30 schools in the United Kingdom were analysed. A new cohort of 1425 Year 1 pupils was recruited in the second year. Over two terms, the experimental group made 1.75 more standardized points progress in reading compared to the control group, a small but significant effect. A replication study in the second year did not elicit the same significant gains. Over five terms, experimental pupils were 11 months ahead on age equivalent reading scores, relative to their chronological age. This study is the first of its type to evaluate the efficacy of a whole school reading programme in the United Kingdom. The findings contribute to an emerging understanding of what pupil progress might be expected as a result of a whole school reading programme

Towards three-dimensional underwater mapping without odometry

This paper presents a method for the creation of three-dimensional maps of underwater cisterns and wells using a submersible robot equipped with two scanning sonars and a compass. Previous work in this area utilized a particle filter to perform offline simultaneous localization and mapping (SLAM) in two dimensions using a single sonar [11]. This work utilizes scan matching and incorporates an additional sonar that scans in a perpendicular plane. Given a set of overlapping horizontal and vertical sonar scans, an algorithm was implemented to map underwater chambers by matching sets of scans using a weighted iterative closest point (ICP) method. This matching process has been augmented to align the features of the underwater cistern data without robot odometry. Results from a swimming pool and an archeological site trials indicate successful mapping is achieved

Dynamic Ocean Management: Defining and Conceptualizing Real-Time Management of the Ocean

Most spatial marine management techniques (e.g., marine protected areas) draw stationary boundaries around often mobile marine features, animals, or resource users. While these approaches can work for relatively stationary marine resources, to be most effective marine management must be as fluid in space and time as the resources and users we aim to manage. Instead, a shift towards dynamic ocean management is suggested, defined as management that rapidly changes in space and time in response to changes in the ocean and its users through the integration of near real-time biological, oceanographic, social and/or economic data. Dynamic management can refine the temporal and spatial scale of managed areas, thereby better balancing ecological and economic objectives. Temperature dependent habitat of a hypothetical mobile marine species was simulated to show the efficiency of dynamic management, finding that 82.0 to 34.2 percent less area needed to be managed using a dynamic approach. Dynamic management further complements existing management by increasing the speed at which decisions are implemented using predefined protocols. With advances in data collection and sharing, particularly in remote sensing, animal tracking, and mobile technology, managers are poised to apply dynamic management across numerous marine sectors. Existing examples demonstrate that dynamic management can successfully allow managers to respond rapidly to changes on-the-water, however to implement dynamic ocean management widely, several gaps must be filled. These include enhancing legal instruments, incorporating ecological and socioeconomic considerations simultaneously, developing ‘out-of-the-box’ platforms to serve dynamic management data to users, and developing applications broadly across additional marine resource sectors

Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection

The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little is known about the functional capacity of these lymphocytes, which could provide insights into mechanisms of failure of viral control and liver damage in this setting. We compared the effector function of total circulating and intrahepatic CD8 T cells in CHB patients and healthy donors. We demonstrated that CD8 T cells from CHB patients, regardless of their antigen specificity, were impaired in their ability to produce interleukin-2 and proliferate upon TCR-dependent stimulation. In contrast, these CD8 T cells had preserved production of the proinflammatory cytokines interferon-γ and tumor necrosis factor-α. This aberrant functional profile was partially attributable to down-regulation of the proximal T cell receptor signaling molecule CD3ζ, and could be corrected in vitro by transfection of CD3ζ or replenishment of the amino acid arginine required for its expression. We provide evidence for depletion of arginine in the inflamed hepatic microenvironment as a potential mechanism for these defects in global CD8 T cell signaling and function. These data imply that polarized CD8 T cells within the HBV-infected liver may impede proliferative antiviral effector function, while contributing to the proinflammatory cytokine environment

The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects

Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) – an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid – to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay

<p>Abstract</p> <p>Background</p> <p>Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.</p> <p>Methods</p> <p>All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.</p> <p>Results</p> <p>Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.</p> <p>Conclusions</p> <p>We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.</p

Frozen magma lenses below the oceanic crust

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 436 (2005): 1149-1152, doi:10.1038/nature03944.The Earth's oceanic crust crystallizes from magmatic systems generated at mid-ocean ridges. Whereas a single magma body residing within the mid-crust is thought to be responsible for the generation of the upper oceanic crust, it remains unclear if the lower crust is formed from the same magma body, or if it mainly crystallizes from magma lenses located at the base of the crust. Thermal modelling, tomography, compliance and wide-angle seismic studies, supported by geological evidence, suggest the presence of gabbroic-melt accumulations within the Moho transition zone in the vicinity of fast- to intermediate-spreading centres. Until now, however, no reflection images have been obtained of such a structure within the Moho transition zone. Here we show images of groups of Moho transition zone reflection events that resulted from the analysis of approximately 1,500 km of multichannel seismic data collected across the intermediate-spreading-rate Juan de Fuca ridge. From our observations we suggest that gabbro lenses and melt accumulations embedded within dunite or residual mantle peridotite are the most probable cause for the observed reflectivity, thus providing support for the hypothesis that the crust is generated from multiple magma bodies