The latest Permian mass extinction (LPME) was triggered by magmatism of the Siberian Traps Large Igneous Province (STLIP), which left an extensive record of sedimentary Hg anomalies at Northern ...Hemisphere and tropical sites. Here, we present Hg records from terrestrial sites in southern Pangea, nearly antipodal to contemporaneous STLIP activity, providing insights into the global distribution of volcanogenic Hg during this event and its environmental processing. These profiles (two from Karoo Basin, South Africa; two from Sydney Basin, Australia) exhibit significant Hg enrichments within the uppermost Permian extinction interval as well as positive Δ
Hg excursions (to ~0.3‰), providing evidence of long-distance atmospheric transfer of volcanogenic Hg. These results demonstrate the far-reaching effects of the Siberian Traps as well as refine stratigraphic placement of the LPME interval in the Karoo Basin at a temporal resolution of ~10
years based on global isochronism of volcanogenic Hg anomalies.
The early evolutionary history of Ornithodira (avian-line archosaurs) has hitherto been documented by incomplete (Lagerpeton) or unusually specialized forms (pterosaurs and Silesaurus). Recently, a ...variety of Silesaurus-like taxa have been reported from the Triassic period of both Gondwana and Laurasia, but their relationships to each other and to dinosaurs remain a subject of debate. Here we report on a new avian-line archosaur from the early Middle Triassic (Anisian) of Tanzania. Phylogenetic analysis places Asilisaurus kongwe gen. et sp. nov. as an avian-line archosaur and a member of the Silesauridae, which is here considered the sister taxon to Dinosauria. Silesaurids were diverse and had a wide distribution by the Late Triassic, with a novel ornithodiran bauplan including leaf-shaped teeth, a beak-like lower jaw, long, gracile limbs, and a quadrupedal stance. Our analysis suggests that the dentition and diet of silesaurids, ornithischians and sauropodomorphs evolved independently from a plesiomorphic carnivorous form. As the oldest avian-line archosaur, Asilisaurus demonstrates the antiquity of both Ornithodira and the dinosaurian lineage. The initial diversification of Archosauria, previously documented by crocodilian-line archosaurs in the Anisian, can now be shown to include a contemporaneous avian-line radiation. The unparalleled taxonomic diversity of the Manda archosaur assemblage indicates that archosaur diversification was well underway by the Middle Triassic or earlier.
Earth's largest biotic crisis occurred during the Permo-Triassic Transition (PTT). On land, this event witnessed a turnover from synapsid- to archosauromorph-dominated assemblages and a restructuring ...of terrestrial ecosystems. However, understanding extinction patterns has been limited by a lack of high-precision fossil occurrence data to resolve events on submillion-year timescales. We analyzed a unique database of 588 fossil tetrapod specimens from South Africa's Karoo Basin, spanning ∼4 My, and 13 stratigraphic bin intervals averaging 300,000 y each. Using sample-standardized methods, we characterized faunal assemblage dynamics during the PTT. High regional extinction rates occurred through a protracted interval of ∼1 Ma, initially co-occurring with low origination rates. This resulted in declining diversity up to the acme of extinction near the
-
Assemblage Zone boundary. Regional origination rates increased abruptly above this boundary, co-occurring with high extinction rates to drive rapid turnover and an assemblage of short-lived species symptomatic of ecosystem instability. The "disaster taxon"
shows a long-term trend of increasing abundance initiated in the latest Permian.
comprised 54% of all specimens by the onset of mass extinction and 70% in the extinction aftermath. This early
abundance suggests its expansion was facilitated by environmental changes rather than by ecological opportunity following the extinctions of other species as commonly assumed for disaster taxa. Our findings conservatively place the Karoo extinction interval closer in time, but not coeval with, the more rapid marine event and reveal key differences between the PTT extinctions on land and in the oceans.
The relationship between dinosaurs and other reptiles is well established, but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional ...morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies or are known from poorly preserved or incomplete material. Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird-crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.
Sauropodomorph dinosaurs dominated the herbivorous niches during the first 40 million years of dinosaur history (Late Triassic-Early Jurassic), yet palaeobiological factors that influenced their ...evolutionary success are not fully understood. For instance, knowledge on their behaviour is limited, although herding in sauropodomorphs has been well documented in derived sauropods from the Late Jurassic and Cretaceous. Here we report an exceptional fossil occurrence from Patagonia that includes over 100 eggs and skeletal specimens of 80 individuals of the early sauropodomorph Mussaurus patagonicus, ranging from embryos to fully-grown adults, with an Early Jurassic age as determined by high-precision U-Pb zircon geochronology. Most specimens were found in a restricted area and stratigraphic interval, with some articulated skeletons grouped in clusters of individuals of approximately the same age. Our new discoveries indicate the presence of social cohesion throughout life and age-segregation within a herd structure, in addition to colonial nesting behaviour. These findings provide the earliest evidence of complex social behaviour in Dinosauria, predating previous records by at least 40 My. The presence of sociality in different sauropodomorph lineages suggests a possible Triassic origin of this behaviour, which may have influenced their early success as large terrestrial herbivores.
Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG trinucleotide repeat expansion in
, resulting in a mutant huntingtin protein. IONIS-HTT
(hereafter, HTT
) is an ...antisense oligonucleotide designed to inhibit
messenger RNA and thereby reduce concentrations of mutant huntingtin.
We conducted a randomized, double-blind, multiple-ascending-dose, phase 1-2a trial involving adults with early Huntington's disease. Patients were randomly assigned in a 3:1 ratio to receive HTT
or placebo as a bolus intrathecal administration every 4 weeks for four doses. Dose selection was guided by a preclinical model in mice and nonhuman primates that related dose level to reduction in the concentration of huntingtin. The primary end point was safety. The secondary end point was HTT
pharmacokinetics in cerebrospinal fluid (CSF). Prespecified exploratory end points included the concentration of mutant huntingtin in CSF.
Of the 46 patients who were enrolled in the trial, 34 were randomly assigned to receive HTT
(at ascending dose levels of 10 to 120 mg) and 12 were randomly assigned to receive placebo. Each patient received all four doses and completed the trial. Adverse events, all of grade 1 or 2, were reported in 98% of the patients. No serious adverse events were seen in HTT
-treated patients. There were no clinically relevant adverse changes in laboratory variables. Predose (trough) concentrations of HTT
in CSF showed dose dependence up to doses of 60 mg. HTT
treatment resulted in a dose-dependent reduction in the concentration of mutant huntingtin in CSF (mean percentage change from baseline, 10% in the placebo group and -20%, -25%, -28%, -42%, and -38% in the HTT
10-mg, 30-mg, 60-mg, 90-mg, and 120-mg dose groups, respectively).
Intrathecal administration of HTT
to patients with early Huntington's disease was not accompanied by serious adverse events. We observed dose-dependent reductions in concentrations of mutant huntingtin. (Funded by Ionis Pharmaceuticals and F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02519036.).
Reversed phase liquid chromatography using superheated water as the mobile phase, at temperatures between 100 and 250
°C, offers a number of advantages for the analyst. It is an environmentally clean ...solvent, reducing solvent usage and disposal costs. It has advantages in detection, allowing UV spectra to be monitored down to short wavelengths, as well as a compatibility with universal flame ionisation detection and mass spectroscopy. By employing deuterium oxide as the eluent, solvent free NMR spectra can be measured. The development of newer more thermally stable stationary phases, including hybrid phases, have expanded the analytes that can be examined and these now range from alkylbenzenes, phenols, alkyl aryl ketones and a number of pharmaceuticals to carboxylic acids, amino acids, and carbohydrates. Very few compounds have been found to be unstable during the analysis.
The separation methods can be directly coupled to superheated water extraction providing a totally solvent free system for sample extraction and analysis.
The Zwicky Transient Facility: Observing System Dekany, Richard; Smith, Roger M.; Riddle, Reed ...
Publications of the Astronomical Society of the Pacific,
03/2020, Letnik:
132, Številka:
1009
Journal Article
Recenzirano
Odprti dostop
The Zwicky Transient Facility (ZTF) Observing System (OS) is the data collector for the ZTF project to study astrophysical phenomena in the time domain. ZTF OS is based upon the 48 inch aperture ...Schmidt-type design Samuel Oschin Telescope at the Palomar Observatory in Southern California. It incorporates new telescope aspheric corrector optics, dome and telescope drives, a large-format exposure shutter, a flat-field illumination system, a robotic bandpass filter exchanger, and the key element: a new 47-square-degree, 600 megapixel cryogenic CCD mosaic science camera, along with supporting equipment. The OS collects and delivers digitized survey data to the ZTF Data System (DS). Here, we describe the ZTF OS design, optical implementation, delivered image quality, detector performance, and robotic survey efficiency.
Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading of α-syn pathology is believed to contribute to ...disease progression, immunotherapy with antibodies directed against α-syn is considered a promising therapeutic approach for slowing disease progression. Here we report the identification, binding characteristics, and efficacy in PD mouse models of the human-derived α-syn antibody BIIB054, which is currently under investigation in a Phase 2 clinical trial for PD. BIIB054 was generated by screening human memory B-cell libraries from healthy elderly individuals. Epitope mapping studies conducted using peptide scanning, X-ray crystallography, and mutagenesis show that BIIB054 binds to α-syn residues 1–10. BIIB054 is highly selective for aggregated forms of α-syn with at least an 800-fold higher apparent affinity for fibrillar versus monomeric recombinant α-syn and a strong preference for human PD brain tissue. BIIB054 discriminates between monomers and oligomeric/fibrillar forms of α-syn based on high avidity for aggregates, driven by weak monovalent affinity and fast binding kinetics. In efficacy studies in three different mouse models with intracerebrally inoculated preformed α-syn fibrils, BIIB054 treatment attenuated the spreading of α-syn pathology, rescued motor impairments, and reduced the loss of dopamine transporter density in dopaminergic terminals in striatum. The preclinical data reported here provide a compelling rationale for clinical development of BIIB054 for the treatment and prevention of PD.
•Identification of an aggregate selective human-derived antibody to α-synuclein.•BIIB054 shows ≥800-fold higher binding to aggregates than monomer.•Structure activity relationship of the BIIB054/α-synuclein complex.•BIIB054 treatment in mice reduces spread of pathology and improves motor function.
The importance of sample preparation methods as the first stage in an analytical procedure is emphasised and examined. Examples are given of the extraction and concentration of analytes from solid, ...liquid and gas phase matrices, including solvent phase extractions, such as supercritical fluids and superheated water extraction, solid-phase extraction and solid-phase microextraction, headspace analysis and vapour trapping. The potential role of selective extraction methods, including molecular imprinted phases and affinity columns, are considered. For problem samples alternative approaches, such as derivatisation are discussed, and potential new approaches minimising sample preparation are noted.
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