64 research outputs found
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Raymond Gibson (1938â2023): in memoriam
On 29 January 2023, Raymond (Ray) Gibson (Fig. 1), Professor Emeritus of Liverpool John Moores University, died in a hospital on the Wirral. He lived a very busy life, rich in travels and scientific discoveries, and he was one of the most authoritative world experts in the taxonomy of nemerteans. Ray was born on 23 November 1938 in Catterick Village in Yorkshire. He gained his Private Pilotâs License aged 17 and had several adventures in the small plane. In 1965 after leaving the Royal Airforce as a qualified pilot he got his B.Sc. in Zoology First class degree from Leeds University and in 1968 gained his Ph.D. from Leeds University. Ray began his interest in nemerteans when he was a student at Leeds University. His Ph.D. supervisor was Dr. Joe Jennings, who at the time was researching the nutrition and digestion of nemerteans and âturbellariansâ (a grade of free-living platyhelminths). Rayâs first articles on the nutrition and biology of Malacobdella grossa were published when he was at Leeds University (Gibson 1967, 1968; Gibson & Jennings 1969). In 1971 Ray joined the Liverpool Regional College of Technology (this became Liverpool Polytechnic and then Liverpool John Moores University), where he worked for 30 years. His first book (Gibson 1972) is an excellent summary of knowledge on nemertean biology at the time and has âentangledâ (rather than âhookedâ) young students worldwide in the following generations into this field. Rayâs exploratory enthusiasm was unmatched. He would come early in the morning and spend the day in concentrated writing, microscopy, or figure preparation. An ashtray was ever present next to his microscope and cigarettes and black coffee were all he needed to sustain him through the long days. For a long time, the histology unit was complete with the all-pervasive smell of xylene. He supervised post-graduates from many countries and backgrounds, teaching them the intricacies of paraffin sectioning and histochemistry.Peer reviewe
The Phylum Cnidaria and Investigations of Its Toxins and Venoms Until 1990
Cnidarians are the largest phylum of generally toxic animals, yet their toxins and venoms have not received as much scientific attention as those of many terrestrial (snakes, scorpions, spiders, etc.) and even some marine animals (i.e. cone snails). Approximately 13,000 living cnidarian species have been described by systematists. A major rationale for their study in the past, besides scientific curiousity, was to better treat victims of their envenomation. While that goal remains a high priority, it is now appreciated that the toxins of these mostly marine animals can be very useful molecular probes for the analysis of ion channels involved in electrical signaling, immune responses and other signal transduction processes of biomedical interest. For instance, anaphylaxis was discovered by Richet (1905) during experiments with sea anemone and hydrozoan tentacular extracts. Similarly, it has recently been shown that a toxin from another sea anemone is able to potently inhibit T-lymphocyte proliferation in models of certain autoimmune diseases. Thus, these natural substances continue to be of relevance for understanding and treating human diseases. In addition to introducing phylum Cnidaria (Coelenterata), we provide a short history of early (until about 1990) research on cnidarian toxins and venoms, to provide a perspective for appreciating the scientific advances of the past two decades that are summarized in the ensuing 19 papers in this special Toxicon issue
Discovery of the Nicotinic Receptor Toxin Anabaseine in a <i>Polystiliferan</i> Nemertean
Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators. Hoplonemerteans have a proboscis armed with one or more stylets used in prey capture and are taxonomically divided into Order Monostilifera, whose members possess a single large proboscis stylet, and Order Polystilifera, whose members have multiple small stylets. Many monostiliferans contain alkaloidal toxins, including anabaseine, that stimulate and then desensitize nicotinic acetylcholine receptors that are present in all animals. These compounds also interact with pyridyl chemoreceptors in crustaceans, reducing predation and larval settlement. Anabaseine has been a lead compound in the design of alpha7 nicotinic acetylcholine receptor agonists like GTS-21 (also called DMXBA) to treat disorders of cognition such as Alzheimerâs disease and schizophrenia. These drug candidates also display anti-inflammatory activities of potential medical importance. Most polystiliferans live deep in open oceans and are relatively inaccessible. We fortunately obtained two live specimens of a large benthic polystiliferan, Paradrepanophorus crassus (Pc), from the coast of Spain. MS and NMR analyses of the Ehrlichâs reagent derivative allowed identification of anabaseine. A spectrophotometric assay for anabaseine, also based on its reaction with Ehrlichâs reagent, revealed high concentrations of anabaseine in the body and proboscis. Apparently, the biosynthetic mechanism for producing anabaseine was acquired early in the evolution of the Hoplonemertea, before the monostiliferan-polystiliferan divergence
Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids
Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 ”M and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic
Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal α7 nicotinic acetylcholine receptor
The pentameric acetylcholine-binding protein (AChBP) is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of aromatic side chains contributed by loops C and F on opposing faces of each subunit interface. Crystal structures of Aplysia AChBP bound with the agonist anabaseine, two partial agonists selectively activating the α7 receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy metabolite, and an indole-containing partial agonist, tropisetron, were solved at 2.7â1.75 Ă
resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen bond acceptor for the agonist-protonated nitrogen. In the partial agonist complexes, the benzylidene and indole substituent positions, dictated by tight interactions with loop F, preclude loop C from adopting the closed conformation seen for full agonists. Fluctuation in loop C position and duality in ligand binding orientations suggest molecular bases for partial agonism at full-length receptors. This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template region for designing α7-selective partial agonists to treat cognitive deficits in mental and neurodegenerative disorders
Activation and Desensitization of Nicotinic α7-type Acetylcholine Receptors by Benzylidene Anabaseines and Nicotine
Nicotinic receptor activation is inextricably linked to desensitization.
This duality affects our ability to develop useful therapeutics targeting
nicotinic acetylcholine receptor (nAChR). Nicotine and some α7-selective
experimental partial agonists produce a transient activation of α7
receptors followed by a period of prolonged residual inhibition or
desensitization (RID). The object of the present study was to determine
whether RID was primarily due to prolonged desensitization or due to channel
block. To make this determination, we used agents that varied significantly in
their production of RID and two α7-selective positive allosteric
modulators (PAMs): 5-hydroxyindole (5HI), a type 1 PAM that does not prevent
desensitization; and
1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea
(PNU-120596), a type 2 PAM that reactivates desensitized receptors. The
RID-producing compounds nicotine and 3-(2,4-dimethoxybenzylidene)anabaseine
(diMeOBA) could obscure the potentiating effects of 5HI. However, through the
use of nicotine, diMeOBA, and the RID-negative compound
3-(2,4-dihydroxybenzylidene)anabaseine (diOHBA) in combination with
PNU-120596, we confirmed that diMeOBA produces short-lived channel block of
α7 but that RID is because of the induction of a desensitized state that
is stable in the absence of PNU-120596 and activated in the presence of
PNU-120596. In contrast, diOHBA produced channel block but only readily
reversible desensitization, whereas nicotine produced desensitization that
could be converted into activation by PNU-120596 but no demonstrable channel
block. Steady-state currents through receptors that would otherwise be
desensitized could also be produced by the application of PNU-120596 in the
presence of a physiologically relevant concentration of choline (60 ÎŒM),
which may be significant for the therapeutic development of type 2 PAMs
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