First Detection of Mycobacterium ulcerans DNA in Environmental Samples from South America

The occurrences of many environmentally-persistent and zoonotic infections are driven by ecosystem changes, which in turn are underpinned by land-use modifications that alter the governance of pathogen, biodiversity and human interactions. Our current understanding of these ecological changes on disease emergence however remains limited. Buruli ulcer is an emerging human skin disease caused by the mycobacterium, Mycobacterium ulcerans, for which the exact route of infection remains unclear. It can have a devastating impact on its human host, causing extensive necrosis of the skin and underlying tissue, often leading to permanent disability. The mycobacterium is associated with tropical aquatic environments and incidences of the disease are significantly higher on floodplains and where there is an increase of human aquatic activities. Although the disease has been previously diagnosed in South America, until now the presence of M. ulcerans DNA in the wild has only been identified in Australia where there have been significant outbreaks and in western and central regions of Africa where the disease is persistent. Here for the first time, we have identified the presence of the aetiological agent's DNA in environmental samples from South America. The DNA was positively identified using Real-time Polymerase Chain Reaction (PCR) on 163 environmental samples, taken from 23 freshwater bodies in French Guiana (Southern America), using primers for both IS2404 and for the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes (KR). Five samples out of 163 were positive for both primers from three different water bodies. A further nine sites had low levels of IS2404 close to a standard CT of 35 and could potentially harbour M. ulcerans. The majority of our positive samples (8/14) came from filtered water. These results also reveal the Sinnamary River as a potential source of infection to humans. © 2014 Morris et al

Genetic Diversity of PCR-Positive, Culture-Negative and Culture-Positive Mycobacterium ulcerans Isolated from Buruli Ulcer Patients in Ghana.

Culture of Mycobacterium ulcerans from Buruli ulcer patients has very low sensitivity. Thus confirmation of M. ulcerans infection is primarily based on PCR directed against IS2404. In this study we compare the genotypes obtained by variable number of tandem repeat analysis of DNA from IS2404-PCR positive cultures with that obtained from IS2404 positive, culture-negative tissue. A significantly greater genetic heterogeneity was found among culture-negative samples compared with that found in cultured strains but a single genotype is over-represented in both sample sets. This study provides evidence that both the focal location of bacteria in a lesion as well as differences in the ability to culture a particular genotype may underlie the low sensitivity of culture. Though preliminary, data from this work also suggests that mycobacteria previously associated with fish disease (M. pseudoshottsii) may be pathogenic for humans

A continuum from clear to cloudy hot-Jupiter exoplanets without primordial water depletion

PublishedLetterThousands of transiting exoplanets have been discovered, but spectral analysis of their atmospheres has so far been dominated by a small number of exoplanets and data spanning relatively narrow wavelength ranges (such as 1.1 to 1.7 μm). Recent studies show that some hot- Jupiter exoplanets have much weaker water absorption features in their near-infrared spectra than predicted. The low amplitude of water signatures could be explained by very low water abundances, which may be a sign that water was depleted in the protoplanetary disk at the planet’s formation location, but it is unclear whether this level of depletion can actually occur. Alternatively, these weak signals could be the result of obscuration by clouds or hazes, as found in some optical spectra. Here we report results from a comparative study of ten hot Jupiters covering the wavelength range 0.3–5 micrometres, which allows us to resolve both the optical scattering and infrared molecular absorption spectroscopically. Our results reveal a diverse group of hot Jupiters that exhibit a continuum from clear to cloudy atmospheres. We find that the difference between the planetary radius measured at optical and infrared wavelengths is an effective metric for distinguishing different atmosphere types. The difference correlates with the spectral strength of water, so that strong water absorption lines are seen in clear-atmosphere planets and the weakest features are associated with clouds and hazes. This result strongly suggests that primordial water depletion during formation is unlikely and that clouds and hazes are the cause of weaker spectral signatures.European Research Council European Union’s Seventh Framework Programme (FP7/2007-2013)NASACNES and the French Agence Nationale de la Recherche (ANR)UK Science and Technology Facilities Council (STFC)NSFTennessee State UniversityState of Tennesse

Hubble PanCET: An isothermal day-side atmosphere for the bloated gas-giant HAT-P-32Ab

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordWe present a thermal emission spectrum of the bloated hot Jupiter HAT-P-32Ab from a single eclipse observation made in spatial scan mode with the Wide Field Camera 3 (WFC3) aboard the Hubble Space Telescope (HST). The spectrum covers the wavelength regime from 1.123 to 1.644 microns which is binned into 14 eclipse depths measured to an averaged precision of 104 parts-per million. The spectrum is unaffected by a dilution from the close M-dwarf companion HAT-P-32B, which was fully resolved. We complemented our spectrum with literature results and performed a comparative forward and retrieval analysis with the 1D radiative-convective ATMO model. Assuming solar abundance of the planet atmosphere, we find that the measured spectrum can best be explained by the spectrum of a blackbody isothermal atmosphere with Tp = 1995 +/- 17K, but can equally-well be described by a spectrum with modest thermal inversion. The retrieved spectrum suggests emission from VO at the WFC3 wavelengths and no evidence of the 1.4 micron water feature. The emission models with temperature profiles decreasing with height are rejected at a high confidence. An isothermal or inverted spectrum can imply a clear atmosphere with an absorber, a dusty cloud deck or a combination of both. We find that the planet can have continuum of values for the albedo and recirculation, ranging from high albedo and poor recirculation to low albedo and efficient recirculation. Optical spectroscopy of the planet's day-side or thermal emission phase curves can potentially resolve the current albedo with recirculation degeneracy.NN, DKS and TME acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. JG acknowledges support from a Leverhulme Trust Research Project Grant. G.W.H. and M.H.W. acknowledge long-term support from Tennessee State University and the State of Tennessee through its Centers of Excellence program and from the Space Telescope Science Institue under HST-GO-14767. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). DE and VB acknowledge the financial support of the SNSF. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project FOUR ACES; grant agreement No 724427)

Southern Annular Mode drives multicentury wildfire activity in southern South America

The Southern Annular Mode (SAM) is the main driver of climate variability at mid to high latitudes in the Southern Hemisphere, affecting wildfire activity, which in turn pollutes the air and contributes to human health problems and mortality, and potentially provides strong feedback to the climate system through emissions and land cover changes. Here we report the largest Southern Hemisphere network of annually resolved tree ring fire histories, consisting of 1,767 fire-scarred trees from 97 sites (from 22 °S to 54 °S) in southern South America (SAS), to quantify the coupling of SAM and regional wildfire variability using recently created multicentury proxy indices of SAM for the years 1531–2010 AD. We show that at interannual time scales, as well as at multidecadal time scales across 37–54 °S, latitudinal gradient elevated wildfire activity is synchronous with positive phases of the SAM over the years 1665–1995. Positive phases of the SAM are associated primarily with warm conditions in these biomass-rich forests, in which widespread fire activity depends on fuel desiccation. Climate modeling studies indicate that greenhouse gases will force SAM into its positive phase even if stratospheric ozone returns to normal levels, so that climate conditions conducive to widespread fire activity in SAS will continue throughout the 21st century

The effect of long term combined yoga practice on the basal metabolic rate of healthy adults

BACKGROUND: Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. METHODS: The measured BMR of individuals practicing yoga through a combination of practices was compared with that of control subjects who did not practice yoga but led similar lifestyles. RESULTS: The BMR of the yoga practitioners was significantly lower than that of the non-yoga group, and was lower by about 13 % when adjusted for body weight (P < 0.001). This difference persisted when the groups were stratified by gender; however, the difference in BMR adjusted for body weight was greater in women than men (about 8 and 18% respectively). In addition, the mean BMR of the yoga group was significantly lower than their predicted values, while the mean BMR of non-yoga group was comparable with their predicted values derived from 1985 WHO/FAO/UNU predictive equations. CONCLUSION: This study shows that there is a significantly reduced BMR, probably linked to reduced arousal, with the long term practice of yoga using a combination of stimulatory and inhibitory yogic practices

Two Tryptophans Are Better Than One in Accelerating Electron Flow through a Protein

We have constructed and structurally characterized a <i>Pseudomonas aeruginosa</i> azurin mutant <b>Re126WWCu^I</b>, where two adjacent tryptophan residues (W124 and W122, indole separation 3.6–4.1 Å) are inserted between the Cu^I center and a Re photosensitizer coordinated to the imidazole of H126 (Re^I(H126)­(CO)₃(4,7-dimethyl-1,10-phenanthroline)⁺). Cu^I oxidation by the photoexcited Re label (*Re) 22.9 Å away proceeds with a ∼70 ns time constant, similar to that of a single-tryptophan mutant (∼40 ns) with a 19.4 Å Re–Cu distance. Time-resolved spectroscopy (luminescence, visible and IR absorption) revealed two rapid reversible electron transfer steps, W124 → *Re (400–475 ps, <i>K</i>₁ ≅ 3.5–4) and W122 → W124^•+ (7–9 ns, <i>K</i>₂ ≅ 0.55–0.75), followed by a rate-determining (70–90 ns) Cu^I oxidation by W122^•+ ca. 11 Å away. The photocycle is completed by 120 μs recombination. No photochemical Cu^I oxidation was observed in <b>Re126FWCu^I</b>, whereas in <b>Re126WFCu^I</b>, the photocycle is restricted to the ReH126W124 unit and Cu^I remains isolated. QM/MM/MD simulations of <b>Re126WWCu^I</b> indicate that indole solvation changes through the hopping process and W124 → *Re electron transfer is accompanied by water fluctuations that tighten W124 solvation. Our finding that multistep tunneling (hopping) confers a ∼9000-fold advantage over single-step tunneling in the double-tryptophan protein supports the proposal that hole-hopping through tryptophan/tyrosine chains protects enzymes from oxidative damage

An optical transmission spectrum for the ultra-hot Jupiter WASP-121b measured with the Hubble Space Telescope

This is the author accepted manuscript. The final version is available from American Astronomical Society / IOP Publishing via the DOI in this record.We present an atmospheric transmission spectrum for the ultra-hot Jupiter WASP-121b, measured using the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST). Across the 0.47-1 micron wavelength range, the data imply an atmospheric opacity comparable to - and in some spectroscopic channels exceeding - that previously measured at near-infrared wavelengths (1.15-1.65 micron). Wavelength-dependent variations in the opacity rule out a gray cloud deck at a confidence level of 3.8-sigma and may instead be explained by VO spectral bands. We find a cloud-free model assuming chemical equilibrium for a temperature of 1500K and metal enrichment of 10-30x solar matches these data well. Using a free-chemistry retrieval analysis, we estimate a VO abundance of -6.6(-0.3,+0.2) dex. We find no evidence for TiO and place a 3-sigma upper limit of -7.9 dex on its abundance, suggesting TiO may have condensed from the gas phase at the day-night limb. The opacity rises steeply at the shortest wavelengths, increasing by approximately five pressure scale heights from 0.47 to 0.3 micron in wavelength. If this feature is caused by Rayleigh scattering due to uniformly-distributed aerosols, it would imply an unphysically high temperature of 6810+/-1530K. One alternative explanation for the short-wavelength rise is absorption due to SH (mercapto radical), which has been predicted as an important product of non-equilibrium chemistry in hot Jupiter atmospheres. Irrespective of the identity of the NUV absorber, it likely captures a significant amount of incident stellar radiation at low pressures, thus playing a significant role in the overall energy budget, thermal structure, and circulation of the atmosphere.Support for program GO-14767 was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. T.M.E., D.K.S., and N.N. acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. G.W.H. and M.H.W. acknowledge support from Tennessee State University and the State of Tennessee through its Centers of Excellence program. J.S.F. acknowledges funding by the Spanish MINECO grant AYA2016-79425-C3-2-P. J.K.B. is supported by a Royal Astronomical Society Research Fellowship. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). V.B. and D.E. have received funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (project Four Aces; grant agreement no. 724427)

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

The POM Monoclonals: A Comprehensive Set of Antibodies to Non-Overlapping Prion Protein Epitopes

PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrPC in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrPC and PrPSc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrPC. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrPC. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrPSc. Other antibodies immunoprecipitate PrPC, but not PrPSc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrPC and PrPSc. Amino-proximal antibodies were found to react with repetitive PrPC epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays