A cell-permeable biscyclooctyne as a novel probe for the identification of protein sulfenic acids

Reactive oxygen species act as important second messengers in cell signaling and homeostasis through the oxidation of protein thiols. However, the dynamic nature of protein oxidation and the lack of sensitivity of existing molecular probes have hindered our understanding of such reactions; therefore, new tools are required to address these challenges. We designed a bifunctional variant of the strained bicyclo[6.1.0]nonyne (BCN-E-BCN) that enables the tagging of intracellular protein sulfenic acids for biorthogonal copper-free click chemistry. In validation studies, BCN-E-BCN binds the sulfenylated form of the actin-severing protein cofilin, while mutation of the cognate cysteine residues abrogates its binding. BCN-E-BCN is cell permeable and reacts rapidly with cysteine sulfenic acids in cultured cells. Using different azide-tagged conjugates, we demonstrate that BCN-E-BCN can be used in various applications for the detection of sulfenylated proteins. Remarkably, cycloaddition of an azide-tagged fluorophore to BCN-E-BCN labelled proteins produced in vivo can be visualized by fluorescence microscopy to reveal their subcellular localization. These findings demonstrate a novel and multifaceted approach to the detection and trapping of sulfenic acids

Lewis Base-Catalysed Enantioselective Radical Conjugate Addition for the Synthesis of Enantioenriched Pyrrolidinones

We report a catalytic asymmetric protocol for the preparation of chiral pyrrolidinones proceeding via a radical pathway. The chemistry exploits the combination of photoredox catalysis and Lewis base catalysis to realise the first example of asymmetric radical conjugate addition to α,β-unsaturated anhydrides and esters. The reaction is initiated by photoredox activation of N-arylglycines to generate, upon decarboxylation, α-amino radicals. These radicals are then intercepted stereoselectively by α,β-unsaturated acyl ammonium intermediates, whose formation is mastered by a chiral isothiourea organocatalyst. Cyclisation leads to catalyst turnover and formation of enantioenriched pyrrolidinones. The utility of the protocol was demonstrated with application to the synthesis of biologically-active γ-amino butyric acids

Hemiparasitic plant impacts animal and plant communities across four trophic levels

1.Understanding the impact of species on community structure is a fundamental question in ecology. There is a growing body of evidence that suggests that both sub-dominant species and parasites can have a disproportionately large impact. 2.Here we report the impacts of an organism that is both subdominant and parasitic, the hemiparasite Rhinanthus minor. Whilst the impact of parasitic angiosperms on their hosts and, to a lesser degree, co-existing plant species, have been well characterized, much less is known about their impacts on higher trophic levels. 3.We experimentally manipulated field densities of the hemiparasite Rhinanthus minor in a species rich grassland, comparing the plant and invertebrate communities in plots where it was removed, at natural densities or at enhanced densities. 4.Plots with natural and enhanced densities of R. minor had lower plant biomass than plots without the hemiparasite, but enhanced densities almost doubled the abundance of invertebrates within the plots across all trophic levels, with effects evident in herbivores, predators and detritivores. 5.The hemiparasite R. minor, despite being a sub-dominant and transient component within plant communities that it inhabits, has profound effects on four different trophic levels. These effects persist beyond the life of the hemiparasite, emphasizing its role as a keystone species in grassland communitie

Nature versus Nurture: The curved spine of the galaxy cluster X-ray luminosity -- temperature relation

The physical processes that define the spine of the galaxy cluster X-ray luminosity -- temperature (L-T) relation are investigated using a large hydrodynamical simulation of the Universe. This simulation models the same volume and phases as the Millennium Simulation and has a linear extent of 500 h^{-1} Mpc. We demonstrate that mergers typically boost a cluster along but also slightly below the L-T relation. Due to this boost we expect that all of the very brightest clusters will be near the peak of a merger. Objects from near the top of the L-T relation tend to have assembled much of their mass earlier than an average halo of similar final mass. Conversely, objects from the bottom of the relation are often experiencing an ongoing or recent merger.Comment: 8 pages, 7 figures, submitted to MNRA

Joint Optical Flow and Temporally Consistent Semantic Segmentation

The importance and demands of visual scene understanding have been steadily increasing along with the active development of autonomous systems. Consequently, there has been a large amount of research dedicated to semantic segmentation and dense motion estimation. In this paper, we propose a method for jointly estimating optical flow and temporally consistent semantic segmentation, which closely connects these two problem domains and leverages each other. Semantic segmentation provides information on plausible physical motion to its associated pixels, and accurate pixel-level temporal correspondences enhance the accuracy of semantic segmentation in the temporal domain. We demonstrate the benefits of our approach on the KITTI benchmark, where we observe performance gains for flow and segmentation. We achieve state-of-the-art optical flow results, and outperform all published algorithms by a large margin on challenging, but crucial dynamic objects.Comment: 14 pages, Accepted for CVRSUAD workshop at ECCV 201

Interpreting the seasonal cycles of atmospheric oxygen and carbon dioxide concentrations at American Samoa Observatory

We present seven years of atmospheric O2/N2 ratio and CO2 concentration data measured from flask samples collected at American Samoa. These data are unusual, exhibiting higher short-term variability, and seasonal cycles not in phase with other sampling stations. The unique nature of atmospheric data from Samoa has been noted previously from measurements of CO2, methyl chloroform, and ozone. With our O2 data, we observe greater magnitude in the short-term variability, but, in contrast, no clear seasonal pattern to this variability. This we attribute to significant regional sources and sinks existing for O2 in both hemispheres, and a dependence on both the latitudinal and altitudinal origins of air masses. We also hypothesize that some samples exhibit a component of "older" air, demonstrating recirculation of air within the tropics. Our findings could be used to help constrain atmospheric transport models which are not well characterized in tropical regions

Pigmentary keratitis in pugs in the United Kingdom: prevalence and associated features

BACKGROUND: Pigmentary keratitis (PK) is commonly recognised in Pugs, but its aetiology is not completely understood. The aim of this study was to determine the prevalence and associated features of PK in Pugs in the United Kingdom (UK). RESULTS: A total of 210 Pugs (420 eyes) were recruited from 12 UK dog shows and social events. The median age of Pugs recruited was 2.50 years (range 0.25-16.25 years). Pigmentary keratitis was detected in 369/420 (87.8%) eyes and in at least one eye 193/210 (91.9%) Pugs, of which 17/193 (8.8%) were affected unilaterally and 176/193 (91.2%) bilaterally. Pigmentary keratitis was typically mild to moderate (46.3 and 49.9% of eyes, respectively). Detection of PK was significantly associated with increased age (P = 0.002) and the presence of medial entropion of the lower eyelid (MELE) (P = 0.001). Severity of PK was significantly associated with the grade of MELE (P &lt; 0.001). There was also a correlation between the presence of limbal pigment and PK (P = 0.036) that warrants further study. CONCLUSIONS: This study estimated a high disease prevalence of PK in UK Pugs, and demonstrated significant associations with age and the presence of MELE. These associations, which have not been previously reported, offer an insight into the underlying pathophysiology of this condition in Pugs. The results encourage further population research, such as prospective longitudinal studies. These findings also support the development of clinical and breeding strategies based on the reduction of MELE and, possibly, limbal pigment.</p

A PCA-based automated finder for galaxy-scale strong lenses

We present an algorithm using Principal Component Analysis (PCA) to subtract galaxies from imaging data, and also two algorithms to find strong, galaxy-scale gravitational lenses in the resulting residual image. The combined method is optimized to find full or partial Einstein rings. Starting from a pre-selection of potential massive galaxies, we first perform a PCA to build a set of basis vectors. The galaxy images are reconstructed using the PCA basis and subtracted from the data. We then filter the residual image with two different methods. The first uses a curvelet (curved wavelets) filter of the residual images to enhance any curved/ring feature. The resulting image is transformed in polar coordinates, centered on the lens galaxy center. In these coordinates, a ring is turned into a line, allowing us to detect very faint rings by taking advantage of the integrated signal-to-noise in the ring (a line in polar coordinates). The second way of analysing the PCA-subtracted images identifies structures in the residual images and assesses whether they are lensed images according to their orientation, multiplicity and elongation. We apply the two methods to a sample of simulated Einstein rings, as they would be observed with the ESA Euclid satellite in the VIS band. The polar coordinates transform allows us to reach a completeness of 90% and a purity of 86%, as soon as the signal-to-noise integrated in the ring is higher than 30, and almost independent of the size of the Einstein ring. Finally, we show with real data that our PCA-based galaxy subtraction scheme performs better than traditional subtraction based on model fitting to the data. Our algorithm can be developed and improved further using machine learning and dictionary learning methods, which would extend the capabilities of the method to more complex and diverse galaxy shapes