Characterisation of a Desmosterol Reductase Involved in Phytosterol Dealkylation in the Silkworm, Bombyx mori

Most species of invertebrate animals cannot synthesise sterols de novo and many that feed on plants dealkylate phytosterols (mostly C29 and C28) yielding cholesterol (C27). The final step of this dealkylation pathway involves desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol. We now report the molecular characterisation in the silkworm, Bombyx mori, of such a desmosterol reductase involved in production of cholesterol from phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic analysis of putative desmosterol reductases revealed the occurrence of various clades that allowed for the identification of a strong reductase candidate gene in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb) and its heterologous expression in Saccharomyces cerevisae, the recombinant protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD- dependent reaction

The Next Generation Transit Survey (NGTS)

© 2017 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. We describe the Next Generation Transit Survey (NGTS), which is a ground-based project searching for transiting exoplanets orbiting bright stars. NGTS builds on the legacy of previous surveys, most notably WASP, and is designed to achieve higher photometric precision and hence find smaller planets than have previously been detected from the ground. It also operates in red light,maximizing sensitivity to late K and earlyMdwarf stars. The survey specifications call for photometric precision of 0.1 per cent in red light over an instantaneous field of view of 100 deg 2 , enabling the detection of Neptune-sized exoplanets around Sun-like stars and super-Earths around M dwarfs. The survey is carried out with a purpose-built facility at Cerro Paranal, Chile, which is the premier site of the European Southern Observatory (ESO). An array of twelve 20 cm f/2.8 telescopes fitted with back-illuminated deep-depletion CCD cameras is used to survey fields intensively at intermediateGalactic latitudes. The instrument is also ideally suited to ground-based photometric follow-up of exoplanet candidates from space telescopes such as TESS, Gaia and PLATO. We present observations that combine precise autoguiding and the superb observing conditions at Paranal to provide routine photometric precision of 0.1 per cent in 1 h for stars with I-band magnitudes brighter than 13. We describe the instrument and data analysis methods as well as the status of the survey, which achieved first light in 2015 and began full-survey operations in 2016. NGTS data will be made publicly available through the ESO archive

Heat, health, and humidity in Australia's monsoon tropics: a critical review of the problematization of 'heat' in a changing climate

Exposure to heat has killed more people in Australia than all other natural hazards combined. As the climate warms, temperatures are projected to rise substantially, increasing the impact of heat stress and heat illness nation-wide. The relation between heat and health is profoundly complex, however, and is understood differently across multiple sectors. This paper thus provides a critical review of how heat is currently measured and managed in Australia, highlighting how humidity, exposure, and exertion are key elements that are not consistently incorporated into 'problematizations' of heat. The presence or absence of these elements produces different spatial and temporal geographies of danger, as well as different governance practices. In particular, the invisibility of humidity as having a significant impact on heat and health shapes whether Australia's tropical monsoon zone is visible as a region at risk or not, and whether prolonged periods of seasonal heat are treated as dangerous. Similarly, different populations and practices become visible depending on whether the human body (its exposure, exertion, cooling, and hydration) is included in accounts of what constitutes 'heat.' As a result, the outdoor, manual workforce is visible as a population at risk in some accounts but not others. A brief review of key policy areas including housing, public health and work health and safety is presented to demonstrate how specific problematizations of heat are critical to the identification of, and response to, current and future climatic conditions. This has implications for how populations, places, and practices are constituted in the region

Multiwavelength optical and NIR variability analysis of the Blazar PKS 0027-426

We present multiwavelength spectral and temporal variability analysis of PKS 0027-426 using optical griz observations from Dark Energy Survey between 2013 and 2018 and VEILS Optical Light curves of Extragalactic TransienT Events (VOILETTE) between 2018 and 2019 and near-infrared (NIR) JKs observations from Visible and Infrared Survey Telescope for Astronomy Extragalactic Infrared Legacy Survey (VEILS) between 2017 and 2019. Multiple methods of cross-correlation of each combination of light curve provides measurements of possible lags between optical–optical, optical–NIR, and NIR–NIR emission, for each observation season and for the entire observational period. Inter-band time lag measurements consistently suggest either simultaneous emission or delays between emission regions on time-scales smaller than the cadences of observations. The colour–magnitude relation between each combination of filters was also studied to determine the spectral behaviour of PKS 0027-426. Our results demonstrate complex colour behaviour that changes between bluer when brighter, stable when brighter, and redder when brighter trends over different time-scales and using different combinations of optical filters. Additional analysis of the optical spectra is performed to provide further understanding of this complex spectral behaviour

Tolerance to drug-induced cell death favours the acquisition of multidrug resistance in Leishmania

The control of the protozoan parasite Leishmania relies on few drugs with unknown cellular targets and unclear mode of action. Several antileishmanials, however, were shown to induce apoptosis in Leishmania and this death mechanism was further studied in drug-sensitive and drug-resistant Leishmania infantum. In sensitive parasites, antimonials (SbIII), miltefosine (MF) and amphotericin B (AMB), but not paromomycin (PARO), triggered apoptotic cell death associated with reactive oxygen species (ROS). In contrast, Leishmania mutants resistant to SbIII, MF or AMB not only failed to undergo apoptosis following exposure to their respective drugs, but also were more tolerant towards apoptosis induced by other antileishmanials, provided that these killed Leishmania via ROS production. Such tolerance favored the rapid acquisition of multidrug resistance. PARO killed Leishmania in a non-apoptotic manner and failed to produce ROS. PARO resistance neither protected against drug-induced apoptosis nor provided an increased rate of acquisition of resistance to other antileishmanials. However, the PARO-resistant mutant, but not SbIII-, MF- or AMB-resistant mutants, became rapidly cross-resistant to methotrexate, a model drug also not producing ROS. Our results therefore link the mode of killing of drugs to tolerance to cell death and to a facilitated emergence of multidrug resistance. These findings may have fundamental implications in the field of chemotherapeutic interventions

Protection of neurons in the retinal ganglion cell layer against excitotoxicity by the N-acylethanolamine, N-linoleoylethanolamine

R. Scott Duncan1,*, Hua Xin1,*, Daryl L Goad1, Kent D Chapman2,3, Peter Koulen1,31Vision Research Center and Departments of Ophthalmology and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, MO, USA; 2Department of Biological Sciences, University of North Texas, Denton, TX, USA; 3Center for Plant Lipid Research, University of North Texas, Denton, TX, USA *Authors contributed equallyAbstract: Retinal ganglion cell (RGC) death is a hallmark of neurodegenerative diseases and disease processes of the eye, including glaucoma. The protection of RGCs has been an important strategy for combating glaucoma, but little clinical success has been reported to date. One pathophysiological consequence of glaucoma is excessive extracellular glutamate subsequently leading to excitotoxicity in the retina. Endocannabinoids, such as the N-acylethanolamine (NAE), arachidonylethanolamine (NAE 20:4), exhibit neuroprotective properties in some models of neurodegenerative disease. The majority of NAEs, however, are not cannabinoids, and their physiological function is not clear. Here, we determined whether the noncannabinoid NAE, linoleoylethanolamine (NAE18:2), protects neurons in the RGC layer against glutamate excitotoxicity in ex-vivo retina cultures. Using a terminal deoxynucleotidyl transferase-mediated dUTP (2´-deoxyuridine 5´-triphosphate) nick-end labeling (TUNEL) assay, we determined that NAE18:2 reduces the number of apoptotic RGC layer neurons in response to glutamate and conclude that NAE18:2 is a neuroprotective compound with potential for treating glaucomatous retinopathy.Keywords: neuroprotection, glutamate, calcium signaling, immunocytochemistry, eye, vision, glaucoma

Evaluation of tensile strength of tissue adhesives and sutures for clear corneal incisions using porcine and bovine eyes, with a novel standardized testing platform

Simon Kaja, Daryl L Goad, Fatima Ali, Ashley Abraham, R Luke Rebenitsch, Savak Teymoorian, Rohit Krishna, Peter KoulenVision Research Center and Department of Ophthalmology, University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USABackground: Tissue adhesives for ophthalmologic applications were proposed almost 50 years ago, yet to date no adequate tissue glues have been identified that combine strong sealing properties with adequate safety and absence of postsurgical side effects. In recent years, cataract surgeries and Descemet's stripping with endothelial keratoplasty procedures have significantly increased the number of clear corneal incisions performed. One of the obstacles to discovery and development of novel tissue adhesives has been the result of nonstandardized testing of potential tissue glues.Methods: We developed an instrument capable of controlling intraocular pressure in explanted porcine and bovine eyes in order to evaluate sealants, adhesives, and surgical closure methods used in ophthalmic surgery in a controlled, repeatable, and validated fashion. We herein developed and validated our instrument by testing the adhesive properties of cyanoacrylate glue in both porcine and bovine explant eyes.Results: The instrument applied and maintained intraocular pressure through a broad range of physiological intraocular pressures. Cyanoacrylate-based glues showed significantly enhanced sealing properties of clear corneal incisions compared with sutured wounds.Conclusion: This study shows the feasibility of our instrument for reliable and standardized testing of tissue adhesive for ophthalmological surgery.Keywords: manometer, intraocular pressure, applanation tonometry, clear corneal incision, tissue adhesive, ocular surger

Formation of albitite-hosted uranium within IOCG systems: the Southern Breccia, Great Bear magmatic zone, Northwest Territories, Canada

Uranium and polymetallic U mineralization hosted within brecciated albitites occurs one kilometer south of the magnetite-rich Au–Co–Bi–Cu NICO deposit in the southern Great Bear magmatic zone (GBMZ), Canada. Concentrations up to 1 wt% U are distributed throughout a 3 by 0.5 km albitization corridor defined as the Southern Breccia zone. Two distinct U mineralization events are observed. Primary uraninite precipitated with or without pyrite–chalcopyrite ± molybdenite within magnetite–ilmenite–biotite–K-feldspar-altered breccias during high-temperature potassic–iron alteration. Subsequently, pitchblende precipitated in earthy hematite–specular hematite–chlorite veins associated with a low-temperature iron–magnesium alteration. The uraninite-bearing mineralization postdates sodic (albite) and more localized high-temperature potassic–iron (biotite–magnetite ± K-feldspar) alteration yet predates potassic (K-feldspar), boron (tourmaline) and potassic–iron–magnesium (hematite ± K-feldspar ± chlorite) alteration. The Southern Breccia zone shares attributes of the Valhalla (Australia) and Lagoa Real (Brazil) albitite-hosted U deposits but contains greater iron oxide contents and lower contents of riebeckite and carbonates. Potassium, Ni, and Th are also enriched whereas Zr and Sr are depleted with respect to the aforementioned albitite-hosted U deposits. Field relationships, geochemical signatures and available U–Pb dates on pre-, syn- and post-mineralization intrusions place the development of the Southern Breccia and the NICO deposit as part of a single iron oxide alkali-altered (IOAA) system. In addition, this case example illustrates that albitite-hosted U deposits can form in albitization zones that predate base and precious metal ore zones in a single IOAA system and become traps for U and multiple metals once the tectonic regime favors fluid mixing and oxidation-reduction reactions

Effects of secretory products of breast cancer cells on osteoblast-like cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe