Evaluation of the limitations and methods to improve rapid phage-based detection of viable Mycobacterium avium subsp. paratuberculosis in the blood of experimentally infected cattle

Background Disseminated infection and bacteraemia is an underreported and under-researched aspect of Johne’s disease. This is mainly due to the time it takes for Mycobacterium avium subsp. paratuberculosis (MAP) to grow and lack of sensitivity of culture. Viable MAP cells can be detected in the blood of cattle suffering from Johne’s disease within 48 h using peptide-mediated magnetic separation (PMMS) followed by bacteriophage amplification. The aim of this study was to demonstrate the first detection of MAP in the blood of experimentally exposed cattle using the PMMS-bacteriophage assay and to compare these results with the immune response of the animal based on serum ELISA and shedding of MAP by faecal culture. Results Using the PMMS-phage assay, seven out of the 19 (37 %) MAP-exposed animals that were tested were positive for viable MAP cells although very low numbers of MAP were detected. Two of these animals were positive by faecal culture and one was positive by serum ELISA. There was no correlation between PMMS-phage assay results and the faecal and serum ELISA results. None of the control animals (10) were positive for MAP using any of the four detection methods. Investigations carried out into the efficiency of the assay; found that the PMMS step was the limiting factor reducing the sensitivity of the phage assay. A modified method using the phage assay directly on isolated peripheral blood mononuclear cells (without PMMS) was found to be superior to the PMMS isolation step. Conclusions This proof of concept study has shown that viable MAP cells are present in the blood of MAP-exposed cattle prior to the onset of clinical signs. Although only one time point was tested, the ability to detect viable MAP in the blood of subclinically infected animals by the rapid phage-based method has the potential to increase the understanding of the pathogenesis of Johne’s disease progression by warranting further research on the presence of MAP in blood

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two `relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report the discovery of a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decline of its light curve follows the predicted mass accretion rate, and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about 2 million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.Comment: To appear in Nature on May 10, 201

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Discovery of the Onset of Rapid Accretion by a Dormant Massive Black Hole

Massive black holes are believed to reside at the centres of most galaxies. They can be- come detectable by accretion of matter, either continuously from a large gas reservoir or impulsively from the tidal disruption of a passing star, and conversion of the gravitational energy of the infalling matter to light. Continuous accretion drives Active Galactic Nuclei (AGN), which are known to be variable but have never been observed to turn on or off. Tidal disruption of stars by dormant massive black holes has been inferred indirectly but the on- set of a tidal disruption event has never been observed. Here we report the first discovery of the onset of a relativistic accretion-powered jet in the new extragalactic transient, Swift J164449.3+573451. The behaviour of this new source differs from both theoretical models of tidal disruption events and observations of the jet-dominated AGN known as blazars. These differences may stem from transient effects associated with the onset of a powerful jet. Such an event in the massive black hole at the centre of our Milky Way galaxy could strongly ionize the upper atmosphere of the Earth, if beamed towards us.Comment: Submitted to Nature. 4 pages, 3 figures (main paper). 26 pages, 13 figures (supplementary information

The availability of novelty sweets within the high school fringe

Background Reducing sugar consumption is a primary focus of current global public health policy. Achieving 5% of total energy from free sugars will be difficult acknowledging the concentration of free sugars in sugar sweetened beverages, confectionery and as hidden sugars in many savoury items. The expansion of the novelty sweet market in the UK has significant implications for children and young adults as they contribute to dental caries, dental erosion and obesity. Objective To identify the most available types of novelty sweets within the high school fringe in Cardiff, UK and to assess their price range and where and how they were displayed in shops. Subjects and methods Shops within a ten minute walking distance around five purposively selected high schools in the Cardiff aea representing different levels of deprivation were visited. Shops in Cardiff city centre and three supermarkets were also visited to identify the most commonly available novelty sweets. Results The ten most popular novelty sweets identified in these scoping visits were (in descending order): Brain Licker, Push Pop, Juicy Drop, Lickedy Lips, Big Baby Pop, Vimto candy spray, Toxic Waste, Tango candy spray, Brain Blasterz Bitz and Mega Mouth candy spray. Novelty sweets were located on low shelves which were accessible to all age-groups in 73% (14 out of 19) of the shops. Novelty sweets were displayed in the checkout area in 37% (seven out of 19) shops. The price of the top ten novelty sweets ranged from 39p to £1. Conclusion A wide range of acidic and sugary novelty sweets were easily accessible and priced within pocket money range. Those personnel involved in delivering dental and wider health education or health promotion need to be aware of recent developments in children's confectionery. The potential effects of these novelty sweets on both general and dental health require further investigation

Investigation of the erosive potential of sour novelty sweets

Provides a background about the link between acidic beverages and dental erosion. Discusses the potential risk of developing dental erosion upon the frequent consumption of novelty sweets. Provides information which could be used by dental personnel in counselling patients who consume novelty sweets or at risk of developing dental erosion. Abstract Background The expansion of the novelty sweets market in the UK has major potential public health implications in children and young adults as they may cause dental erosion. Objective To investigate the erosive potential of the novelty sweets in term of their physiochemical properties and amount of enamel loss. Subjects and methods The pH of a variety of novelty sweets was tested in vitro using a pH meter and the neutralisable acidity was assessed by titrating the sweets against 0.1M NaOH. The viscosity of the novelty sweets was measured using a rotational viscometer. The wettability of enamel by each sweet was measured using dynamic contact angle analyser. Enamel loss was assessed using contact profilometry. Results The pH ranged from 1.8–3.2, the neutralisable acidity ranged from 9–201 ml of 0.1 NaOH. The viscosity of the novelty sweets that come in liquid form ranged from 2–594 mPa s. The surface enamel erosion ranged from 1.95–15.77 μm and from 2.5–17.6 μm with and without immersing in saliva for 1 hour before immersing in acidic solution respectively. The amount of subsurface enamel loss was ranged from 0.75 to 2.3 μm following ultrasonication at 0 min of acidic attack and from 0.23 to 0.85 μm at 60 minutes of acidic attack while immersed in saliva. The contact angle between enamel surface and four sweet was less than the angle formed between the orange juice and the enamel which caused more wettability of enamel. Conclusion The pH is lower than the critical value for enamel erosion (5.5), high neutralisable acidity and high sugar content strongly suggest that these sweets may cause significant amount of dental erosion clinically. In addition, the degree of wettability of enamel by solution is an important factor to consider in determining the enamel loss caused by acidic solution. Immediate tooth brushing would cause further enamel loss as a result of the mechanical removal of softened enamel. However, it has been suggested that postponing brushing after erosive attack should be reconsidered

Dinosaurs reveal the geographical signature of an evolutionary radiation

Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs’ ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation—when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres