What Makes a Great [Mobile | Digital] Art Exhibition?

Passive reception and consumption of art is a given, in our times. Artists produce. Spectators consume. At the nexus stands the curator who chooses the product and the exhibitor who provides the space for consumers. This natural hierarchy also tends to colonize the digital space. But, in the digital world, much of the functioning of the hierarchy has become democratised. The meeting place of exhibited art moved from the physical to the virtual online. Not everyone can visit, say, Istanbul Modern museum. It ought to be possible in principle for everyone to be able to visit “Istanbul Modern Digital” museum. The next stage of digital democracy, already upon us since early 2010, is the mobile art lover, mobile in the sense of being free from being tied down in one place and being able to choose what to see, where to be, and when to do it: early morning, late at night; in the plane, on the train, in bed, in class. Learning is for everyone. It is what makes us human, to continue to learn. Learning takes place best when one is active. In the context of the Mobile Digital Art Exhibition, we have explored ways in which to enhance the experience of the curator as “everyman” and everyman has potentially the opportunity to construct a mobile digital art exhibition, even one such as the “Museum of Innocence” in the manner as described by Orhan Pamuk. Our hero in this story is the self-curator

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues were also shown to be nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis

Review and update of a Nutrient Transfer model used for estimating nitrous oxide emissions from complex grazed landscapes, and implications for nationwide accounting

In New Zealand, nitrous oxide emissions from grazed hill pastures are estimated using different emission factors for urine and dung deposited on different slope classes. Allocation of urine and dung to each slope class needs to consider the distribution of slope classes within a landscape and animal behavior. The Nutrient Transfer (NT) model has recently been incorporated into the New Zealand Agricultural GHG Inventory Model to account for the allocation of excretal nitrogen (N) to each slope class. In this study, the predictive ability of the transfer function within the NT model was explored using urine deposition datasets collected with urine sensor and GPS tracker technology. Data were collected from three paddocks that had areas in low (24°). The NT model showed a good overall predictive ability for two of the three datasets. However, if the urine emission factors (% of urine N emitted as N2 O-N) were to be further disaggregated to assess emissions from all three slope classes or slope gradients, more precise data would be required to accurately represent the range of landscapes found on farms. We have identified the need for more geospatial data on urine deposition and animal location for farms that are topographically out of the range used to develop the model. These new datasets would provide livestock urine deposition on a more continuous basis across slopes (as opposed to broad ranges), a unique opportunity to improve the performance of the NT model.fals

Generation of intense quasi-electrostatic fields due to deposition of particles accelerated by petawatt-range laser-matter interactions

We demonstrate here for the first time that charge emitted by laser-target interactions at petawatt peak-powers can be efficiently deposited on a capacitor-collector structure far away from the target and lead to the rapid (tens of nanoseconds) generation of large quasi-static electric fields over wide (tens-of-centimeters scale-length) regions, with intensities much higher than common ElectroMagnetic Pulses (EMPs) generated by the same experiment in the same position. A good agreement was obtained between measurements from a classical field-probe and calculations based on particle-flux measurements from a Thomson spectrometer. Proof-of-principle particle-in-cell simulations reproduced the measurements of field evolution in time, giving a useful insight into the charging process, generation and distribution of fields. The understanding of this charging phenomenon and of the related intense fields, which can reach the MV/m order and in specific configurations might also exceed it, is very important for present and future facilities studying laser-plasma-acceleration and inertial-confinement-fusion, but also for application to the conditioning of accelerated charged-particles, the generation of intense electric and magnetic fields and many other multidisciplinary high-power laser-driven processes

Spatial variation of trace metals within intertidal beds of native mussels (Mytilus edulis) and non-native Pacific oysters (Crassostrea gigas): implications for the food web?

Abstract Pollution is of increasing concern within coastal regions and the prevalence of invasive species is also rising. Yet the impact of invasive species on the distribution and potential trophic transfer of metals has rarely been examined. Within European intertidal areas, the non-native Pacific oyster (Crassostrea gigas) is becoming established, forming reefs and displacing beds of the native blue mussel (Mytilus edulis). The main hypothesis tested is that the spatial pattern of metal accumulation within intertidal habitats will change should the abundance and distribution of C. gigas continue to increase. A comparative analysis of trace metal content (cadmium, lead, copper and zinc) in both species was carried out at four shores in south-east England. Metal concentrations in bivalve and sediment samples were determined after acid digestion by inductively coupled plasma-optical emission spectrometry. Although results showed variation in the quantities of zinc, copper and lead (mg m-2) in the two bivalve species, differences in shell thickness are also likely to influence the feeding behaviour of predators and intake of metals. The availability and potential for trophic transfer of metals within the coastal food web, should Pacific oysters transform intertidal habitats, is discussed

Stereoretentive post-translational protein editing

Chemical post-translational methods allow convergent side-chain editing of proteins without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side chains via C–C bond formation, using off-protein carbon-centered C· radicals added to unnatural amino acid radical acceptor (SOMOphile, singly occupied molecular orbital (SOMO)) “tags” such as dehydroalanine, are benign and wide-ranging. However, they also typically create epimeric mixtures of d/l-residues. Here, we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-proteinl-alanyl Cβ· radicals, allows Cβ–Hγ, Cβ–Oγ, Cβ–Seγ, Cβ–Bγ, and Cβ–Cγ bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid precursor. This methodology shows great potential to explore protein side-chain diversity and function and in the construction of useful bioconjugates

Macrocyclization of backbone N -methylated peptides by a prolyl oligopeptidase with a distinctive substrate recognition mechanism †

Macrocyclization and multiple backbone N-methylations can significantly improve the pharmacological properties of peptides. Since chemical synthesis of such compounds is often challenging, enzyme-based production platforms are an interesting option. Here, we characterized OphP, a serine peptidase involved in the cyclization of omphalotins, a group of ribosomally produced dodecapeptides with multiple backbone N-methylations. OphP displays robust peptidase and macrocyclase activity towards multiply α-N-methylated peptides of various lengths and composition derived from the omphalotin precursor protein OphMA. In addition, OphP processes, with lower efficiency, peptides unrelated to OphMA, containing a MeGly, MeAla or Pro residue at the P1 site. Structural analysis reveals that OphP adopts a canonical prolyl oligopeptidase fold but, unlike other enzymes of this enzyme family, recognizes its substrates by their hydrophobic and multiply backbone N-methylated core rather than by the follower peptide. The activity of OphP could be harnessed for the enzymatic production of therapeutic peptides

Towards a more complete quantification of the global carbon cycle

The main components of global carbon budget calculations are the emissions from burning fossil fuels, cement production, and net land-use change, partly balanced by ocean CO2 uptake and CO2 increase in the atmosphere. The difference between these terms is referred to as the residual sink, assumed to correspond to increasing carbon storage in the terrestrial biosphere through physiological plant responses to changing conditions (ΔBphys). It is often used to constrain carbon exchange in global earth-system models. More broadly, it guides expectations of autonomous changes in global carbon stocks in response to climatic changes, including increasing CO2, that may add to, or subtract from, anthropogenic CO2 emissions. However, a budget with only these terms omits some important additional fluxes that are needed to correctly infer ΔBphys. They are cement carbonation and fluxes into increasing pools of plastic, bitumen, harvested-wood products, and landfill deposition after disposal of these products, and carbon fluxes to the oceans via wind erosion and non-CO2 fluxes of the intermediate breakdown products of methane and other volatile organic compounds. While the global budget includes river transport of dissolved inorganic carbon, it omits river transport of dissolved and particulate organic carbon, and the deposition of carbon in inland water bodies. Each one of these terms is relatively small, but together they can constitute important additional fluxes that would significantly reduce the size of the inferred ΔBphys. We estimate here that inclusion of these fluxes would reduce ΔBphys from the currently reported 3.6&thinsp;GtC&thinsp;yr−1 down to about 2.1&thinsp;GtC&thinsp;yr−1 (excluding losses from land-use change). The implicit reduction in the size of ΔBphys has important implications for the inferred magnitude of current-day biospheric net carbon uptake and the consequent potential of future biospheric feedbacks to amplify or negate net anthropogenic CO2 emissions.</p

Lipid-Modulated, Graduated Inhibition of N‑Glycosylation Pathway Priming Suggests Wide Tolerance of ER Proteostasis to Stress

Protein N-glycosylation is a cotranslational modification that takes place in the endoplasmic reticulum (ER). Disruption of this process can result in accumulation of misfolded proteins, known as ER stress. In response, the unfolded protein response (UPR) restores proteostasis or responds by controlling cellular fate, including increased expression of activating transcription factor 4 (ATF4) that can lead to apoptosis. The ability to control and manipulate such a stress pathway could find use in relevant therapeutic areas, such as in treating cancerous states in which the native ER stress response is often already perturbed. The first committed step in the N-glycosylation pathway is therefore a target for potential ER stress modulation. Here, using structure-based design, the scaffold of the natural product tunicamycin allows construction of a panel capable of graduated inhibition of DPAGT1 through lipid-substituent-modulated interaction. The development of a quantitative, high-content, cellular immunofluorescence assay allowed precise determination of downstream mechanistic consequences (through the nuclear localization of key proxy transcription factor ATF4 as a readout of resulting ER stress). Only the most potent inhibition of DPAGT1 generates an ER stress response. This suggests that even low-level background biosynthetic flux toward protein glycosylation is sufficient to prevent response to ER stress. Tuned inhibitors of DPAGT1 also now seemingly successfully decouple protein glycosylation from apoptotic response to ER stress, thereby potentially allowing access to cellular states that operate at the extremes of normal ER stress

Synthetic Studies Toward the Skyllamycins: Total Synthesis and Generation of Simplified Analogues

Herein, we report our synthetic studies toward the skyllamycins, a highly modified class of nonribosomal peptide natural products which contain a number of interesting structural features, including the extremely rare α-OH-glycine residue. Before embarking on the synthesis of the natural products, we prepared four structurally simpler analogues. Access to both the analogues and the natural products first required the synthesis of a number of nonproteinogenic amino acids, including three β-OH amino acids that were accessed from the convenient chiral precursor Garner’s aldehyde. Following the preparation of the suitably protected nonproteinogenic amino acids, the skyllamycin analogues were assembled using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. To access the natural products (skyllamycins A–C) the synthetic route used for the analogues was modified. Specifically, linear peptide precursors containing a C-terminal amide were synthesized via solid-phase peptide synthesis. After cleavage from the resin the N-terminal serine residue was oxidatively cleaved to a glyoxyamide moiety. The target natural products, skyllamycins A–C, were successfully prepared via a final step cyclization with concomitant formation of the unusual α-OH-glycine residue. Purification and spectroscopic comparison to the authentic isolated material confirmed the identity of the synthetic natural products.AR