83 results on '"D Brownstein"'
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2. The affinities of the Late Triassic Cryptovaranoides and the age of crown squamates
- Author
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Chase D. Brownstein, Tiago R. Simões, Michael W. Caldwell, Michael S. Y. Lee, Dalton L. Meyer, and Simon G. Scarpetta
- Subjects
phylogenetics ,divergence times ,squamata ,reptiles ,Triassic ,Cryptovaranoides ,Science - Abstract
Most living reptile diversity is concentrated in Squamata (lizards, including snakes), which have poorly known origins in space and time. Recently, †Cryptovaranoides microlanius from the Late Triassic of the United Kingdom was described as the oldest crown squamate. If true, this result would push back the origin of all major lizard clades by 30–65 Myr and suggest that divergence times for reptile clades estimated using genomic and morphological data are grossly inaccurate. Here, we use computed tomography scans and expanded phylogenetic datasets to re-evaluate the phylogenetic affinities of †Cryptovaranoides and other putative early squamates. We robustly reject the crown squamate affinities of †Cryptovaranoides, and instead resolve †Cryptovaranoides as a potential member of the bird and crocodylian total clade, Archosauromorpha. Bayesian total evidence dating supports a Jurassic origin of crown squamates, not Triassic as recently suggested. We highlight how features traditionally linked to lepidosaurs are in fact widespread across Triassic reptiles. Our study reaffirms the importance of critically choosing and constructing morphological datasets and appropriate taxon sampling to test the phylogenetic affinities of problematic fossils and calibrate the Tree of Life.
- Published
- 2023
- Full Text
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3. Trace fossils on dinosaur bones reveal ecosystem dynamics along the coast of eastern North America during the latest Cretaceous
- Author
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Chase D. Brownstein
- Subjects
Taphonomy ,Cretaceous ,Dinosaurs ,Appalachia ,Theropods ,Crocodyliforms ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Direct evidence of paleoecological processes is often rare when the fossil record is poor, as in the case of the Cretaceous of eastern North America. Here, I describe a femur and partial tibia shaft assignable to theropods from two Late Cretaceous sites in New Jersey. The former, identifiable as the femur of a large ornithomimosaur, bears several scores interpreted as shark feeding traces. The tibia shaft has punctures and flaked bone from the bites of mid-sized crocodyliforms, the first documented occurrence of crocodyliform traces on dinosaur bone from the Maastrichtian of the Atlantic Coastal Plain. The surface of the partial tibia is also littered with indentations interpreted as the traces of invertebrates, revealing a microcosm of biological interaction on the coastal seafloor of the Cretaceous Atlantic Ocean. Massive crocodyliforms, such as Deinosuchus rugosus and the slightly smaller Deltasuchus motherali, maintained the role of terrestrial vertebrate taphonomic process drivers in eastern North America during the Cretaceous. The report of crocodyliform bite marks on the ornithomimosaur tibia shaft in this manuscript reinforces the importance of the role of crocodyliforms in the modification of terrestrial vertebrate remains during the Cretaceous in North America. The preserved invertebrate traces add to the sparse record of the presence of barnacles and other marine invertebrates on dinosaur bone, and the evidence of shark feeding on the ornithomimosaur femur support the “bloat-and-float” model of terrestrial vertebrate fossil deposition in marine deposits from the Cretaceous of eastern North America.
- Published
- 2018
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4. Syngnathoid Evolutionary History and the Conundrum of Fossil Misplacement
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C D Brownstein
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Animal Science and Zoology ,Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
Synopsis Seahorses, pipefishes, trumpetfishes, shrimpfishes, and allies are a speciose, globally distributed clade of fishes that have evolved a large number of unusual body plans. The clade that includes all these forms, Syngnathoidei, has become a model for the study of life history evolution, population biology, and biogeography. Yet, the timeline of syngnathoid evolution has remained highly contentious. This debate is largely attributable to the nature of the syngnathoid fossil record, which is both poorly described and patchy for several major lineages. Although fossil syngnathoids have been used to calibrate molecular phylogenies, the interrelationships of extinct species and their affinities to major living syngnathoid clades have scarcely been quantitatively tested. Here, I use an expanded morphological dataset to reconstruct the evolutionary relationships and clade ages of fossil and extant syngnathoids. Phylogenies generated using different analytical methodologies are largely congruent with molecular phylogenetic trees of Syngnathoidei but consistently find novel placements for several key taxa used as fossil calibrators in phylogenomic studies. Tip-dating of the syngnathoid phylogeny finds a timeline for their evolution that differs slightly from the one inferred using molecular trees but is generally congruent with a post-Cretaceous diversification event. These results emphasize the importance of quantitatively testing the relationships of fossil species, particularly when they are critical to assessing divergence times.
- Published
- 2023
- Full Text
- View/download PDF
5. Hidden species diversity in an iconic living fossil vertebrate
- Author
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Chase D. Brownstein, Daemin Kim, Oliver D. Orr, Gabriela M. Hogue, Bryn H. Tracy, M. Worth Pugh, Randal Singer, Chelsea Myles-McBurney, Jon Michael Mollish, Jeffrey W. Simmons, Solomon R. David, Gregory Watkins-Colwell, Eva A. Hoffman, and Thomas J. Near
- Subjects
Fossils ,Vertebrates ,Fisheries ,Animal Fins ,Animals ,General Agricultural and Biological Sciences ,Agricultural and Biological Sciences (miscellaneous) ,Head - Abstract
Ancient, species-poor lineages persistently occur across the Tree of life. These lineages are likely to contain unrecognized species diversity masked by the low rates of morphological evolution that characterize living fossils. Halecomorphi is a lineage of ray-finned fishes that diverged from its closest relatives before 200 Ma and is represented by only one living species in eastern North America, the bowfin, Amia calva Linnaeus. Here, we use double digest restriction-site-associated DNA sequencing and morphology to illuminate recent speciation in bowfins. Our results support the delimitation of a second living species of Amia , with the timing of diversification dating to the Plio-Pleistocene. This delimitation expands the species diversity of an ancient lineage that is integral to studies of vertebrate genomics and development, yet is facing growing conservation threats driven by the caviar fishery.
- Published
- 2022
6. A tyrannosauroid metatarsus from the Merchantville Formation of Delaware increases the diversity of non-tyrannosaurid tyrannosauroids on Appalachia
- Author
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Chase D. Brownstein
- Subjects
Tyrannosauroidea ,Appalachia ,Dryptosaurus ,Late Cretaceous ,Appalachiosaurus ,Dinosaur biogeography ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
During the Late Cretaceous, the continent of North America was divided into two sections: Laramidia in the west and Appalachia in the east. Although the sediments of Appalachia recorded only a sparse fossil record of dinosaurs, the dinosaur faunas of this landmass were different in composition from those of Laramidia. Represented by at least two taxa (Appalachiosaurus montgomeriensis and Dryptosaurus aquilunguis), partial and fragmentary skeletons, and isolated bones, the non-tyrannosaurid tyrannosauroids of the landmass have attracted some attention. Unfortunately, these eastern tyrants are poorly known compared to their western contemporaries. Here, one specimen, the partial metatarsus of a tyrannosauroid from the Campanian Merchantville Formation of Delaware, is described in detail. The specimen can be distinguished from A. montgomeriensis and D. aquilunguis by several morphological features. As such, the specimen represents a potentially previously unrecognized taxon of tyrannosauroid from Appalachia, increasing the diversity of the clade on the landmass. Phylogenetic analysis and the morphology of the bones suggest the Merchantville specimen is a tyrannosauroid of “intermediate” grade, thus supporting the notion that Appalachia was a refugium for relict dinosaur clades.
- Published
- 2017
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7. Aerodynamically Interacting Vertical-Axis Wind Turbines: Performance Enhancement and Three-Dimensional Flow
- Author
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Ian D. Brownstein, Nathaniel J. Wei, and John O. Dabiri
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3D-PTV ,aerodynamics ,VAWT ,vortex interactions ,wind energy ,Technology - Abstract
This study examined three-dimensional, volumetric mean velocity fields and corresponding performance measurements for an isolated vertical-axis wind turbine (VAWT) and for co- and counter-rotating pairs of VAWTs with varying incident wind direction and turbine spacings. The purpose was to identify turbine configurations and flow mechanisms that can improve the power densities of VAWT arrays in wind farms. All experiments were conducted at a Reynolds number of R e D = 7.3 × 10 4 . In the paired arrays, performance enhancement was observed for both the upstream and downstream turbines. Increases in downstream turbine performance correlate with bluff−body accelerations around the upstream turbine, which increase the incident freestream velocity on the downstream turbine in certain positions. Decreases in downstream turbine performance are determined by its position in the upstream turbine’s wake. Changes in upstream turbine performance are related to variations in the surrounding flow field due to the presence of the downstream rotor. For the most robust array configuration studied, an average 14% increase in array performance over approximately a 50° range of wind direction was observed. Additionally, three-dimensional vortex interactions behind pairs of VAWT were observed that can replenish momentum in the wake by advection rather than turbulent diffusion. These effects and their implications for wind-farm design are discussed.
- Published
- 2019
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- View/download PDF
8. Hidden species diversity in a living fossil vertebrate
- Author
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Chase D. Brownstein, Daemin Kim, Oliver D. Orr, Gabriela M. Hogue, Bryn H. Tracy, M. Worth Pugh, Randal Singer, Chelsea Myles-McBurney, Jon Michael Mollish, Jeffrey W. Simmons, Solomon R. David, Gregory Watkins-Colwell, Eva A. Hoffman, and Thomas J. Near
- Abstract
SummaryAncient, species-poor lineages persistently occur across the Tree of Life. These evolutionarily unique lineages are likely to contain unrecognized species diversity masked by the low rates of morphological evolution that characterize living fossils [1, 2]. Halecomorphi is a major clade of ray-finned fishes that diverged from its closest relatives over 200 million years ago [3, 4] yet is represented by only one recognized living species in eastern North America, the Bowfin Amia calva Linnaeus. Here, we use double digest restriction-site associated DNA (ddRAD) sequencing and high-resolution computed tomography to illuminate recent speciation in the bowfins. Our results support the resurrection of a second living species of Bowfin with the timing of diversification dating to the Pleistocene. In turn, we expand the species diversity of an ancient lineage that is integral to studies of vertebrate genomics and development [2, 3, 5], yet is facing growing conservation threats driven by the caviar fishery [6].
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- 2022
- Full Text
- View/download PDF
9. An elongate hadrosaurid forelimb with biological traces informs the biogeography of the Lambeosaurinae
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Immanuel Bissell and Chase D. Brownstein
- Subjects
Synapomorphy ,010506 paleontology ,animal structures ,geography.geographical_feature_category ,biology ,Coastal plain ,Biogeography ,Paleontology ,Lambeosaurinae ,Western Interior Seaway ,010502 geochemistry & geophysics ,biology.organism_classification ,01 natural sciences ,Cretaceous ,Geography ,Appalachia ,Hadrosaurid ,0105 earth and related environmental sciences - Abstract
Although the fossil record of the Late Cretaceous eastern North American landmass Appalachia is poor compared to that from the American West, it includes material from surprisingly aberrant terrestrial vertebrates that may represent relictual forms persisting in relative isolation until the end of the Mesozoic. One intriguing question is to what extent eastern and western North American faunas interspersed following the closure of the Western Interior Seaway during the Maastrichtian Stage of the Late Cretaceous ca. 70 Ma. Isolated remains from the Atlantic Coastal Plain in New Jersey have been preliminarily identified as the bones of crested lambeosaurine hadrosaurids, a derived clade known from the Cretaceous of Asia, western North America, and Europe, but have not been formally described. We describe the partial forelimb of a large hadrosaurid from the late Maastrichtian New Egypt Formation of New Jersey. The ulna preserves multiple deep scores identifiable as shark feeding marks, and both bones show ovoid and circular marks attributable to invertebrates. This forelimb is very similar to another partial antebrachium from the same area that shows evidence of septic arthritis. Both these specimens and a complete humerus from the same unit are closely comparable to the lower forelimbs of lambeosaurines among hadrosaurid dinosaurs. Although the absence of lambeosaurine synapomorphies observable on the New Egypt Formation forelimbs precludes their definite referral to Lambeosaurinae, they show that a morphotype of large hadrosauromorph with distinctly elongate forelimbs existed in the latest Maastrichtian of eastern North America and allow for a revision of the latest Cretaceous biogeography of crested herbivorous dinosaurs.
- Published
- 2020
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10. Osteology and phylogeny of small-bodied hadrosauromorphs from an end-Cretaceous marine assemblage
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Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,Paleontology ,Osteology ,Phylogenetics ,Assemblage (archaeology) ,Animal Science and Zoology ,Biology ,010603 evolutionary biology ,01 natural sciences ,Ecology, Evolution, Behavior and Systematics ,Cretaceous ,0105 earth and related environmental sciences - Abstract
The timing of non-avian dinosaur decline is one of the most debated subjects in dinosaur palaeontology. Dinosaur faunas from the last few million years of the Mesozoic appear far less diverse than those from earlier in the Cretaceous, a trend that could suggest non-avian dinosaur extinction occurred gradually. However, the limited nature of the latest Cretaceous dinosaur record outside western North America has obscured patterns in dinosaur diversity just before the extinction. Here, I describe two associated skeletons and several isolated fossils recovered from the New Egypt Formation of New Jersey, a latest Maastrichtian unit that underlies the K–Pg boundary. The larger skeleton appears to be a small-bodied adult from a lineage outside Hadrosauridae, the dominant group of these animals during the Maastrichtian, that persisted along the eastern coast of North America. Smaller specimens are identifiable as juvenile hadrosauromorphs. These results substantiate an important assemblage of herbivorous dinosaurs from the poorly-known Cretaceous of eastern North America. The marine depositional setting for these skeletons demonstrates that proposed ecosystem preferences among hadrosauromorphs may be biased by post-mortem transportation, and the adult skeleton has implications for assessing the proposed relictual nature of Late Cretaceous eastern North American vertebrates.
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- 2020
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11. Dromaeosaurid crania demonstrate the progressive loss of facial pneumaticity in coelurosaurian dinosaurs
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Chase D. Brownstein
- Subjects
0106 biological sciences ,0303 health sciences ,03 medical and health sciences ,Crania ,biology ,Animal Science and Zoology ,Anatomy ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology - Abstract
Dinosaurs are notable for their extensive skeletal pneumaticity, a feature that may have helped facilitate the development of various ‘extreme’ body plans in this group. Despite its relevance to understanding the evolution of the avian body plan, this feature has only been described in detail for a few non-avian dinosaurs, and cranial pneumaticity outside the braincase remains poorly documented. I describe facial pneumatic features in members of the Dromaeosauridae, a clade of hypercarnivorous dinosaurs closely allied to birds. Variation in the pneumaticity of the nasals and jugals, the position and shape of the pneumatic fenestrae of the maxilla and the border of the antorbital fossa shows that facial pneumaticity differed substantially among closely related dromaeosaurids and other bird-like dinosaurs. Ancestral state reconstructions of facial pneumaticity in coelurosaurs suggest a complex evolutionary history for these features. Surprisingly, the general trend along the path towards birds was the loss or reduction of superficial pneumatic features on the snout and cheek. Some facial pneumatic features seem to have evolved secondarily in some derived bird-like forms. The results show superficial facial pneumaticity did not increase in coelurosaurs and emphasize the complexity of the evolution of pneumatization in the lineage leading to birds.
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- 2020
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12. A JURASSIC STEM-GEKKOTAN FROM THE MORRISON FORMATION REVEALED VIA COMPUTED TOMOGRAPHY IMAGING
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Dalton Meyer, Chase D. Brownstein, and Jacques Gauthier
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medicine.diagnostic_test ,medicine ,Morrison Formation ,Computed tomography ,Anatomy ,Geology - Published
- 2021
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13. Author Correction: Halszkaraptor escuilliei and the evolution of the paravian bauplan
- Author
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Chase D. Brownstein
- Subjects
Multidisciplinary ,lcsh:R ,lcsh:Medicine ,Biological Evolution ,Bone and Bones ,Dinosaurs ,Hindlimb ,Birds ,Forelimb ,Cervical Vertebrae ,Morphogenesis ,Animals ,lcsh:Q ,lcsh:Science ,Author Correction ,Phylogeny - Abstract
The evolution of birds from dinosaurs is a subject that has received great attention among vertebrate paleontologists. Nevertheless, the early evolution of the paravians, the group that contains birds and their closest non-avian dinosaur relatives, remains very poorly known. Even the most basal members of one paravian lineage, the Dromaeosauridae, already show a body plan that differs substantially from their closest non-paravian relatives. Recently, the dromaeosaurid Halszkaraptor escuilliei was described from the Cretaceous of Mongolia. Halszkaraptor possesses numerous unserrated premaxillary teeth, a platyrostral rostrum with a developed neurovascular system, an elongate neck, bizarrely-proportioned forearms, and a foreword-shifted center of mass, differing markedly from other paravians. A reevaluation of the anatomy, taphonomy, environmental setting, and phylogenetic position of H. escuilliei based on additional comparisons with other maniraptorans suggests that, rather than indicating it was a semiaquatic piscivore, the body plan of this dinosaur bears features widely distributed among maniraptorans and in some cases intermediate between the conditions in dromaeosaurids and related clades. I find no evidence for a semiaquatic lifestyle in Halszkaraptor. A phylogenetic reevaluation of Halszkaraptorinae places it as the sister clade to Unenlagiinae, indicating the bizarre features of unenlagiines previously interpreted as evidence of piscivory may also represent a mosaic of plesiomorphic, derived, and intermediate features. The anatomy of Halszkaraptor reveals that dromaeosaurids still possessed many features found in more basal maniraptoran and coelurosaur clades, including some that may have been tied to herbivory. Rather than being a semiaquatic piscavore, Halszkaraptor was a basal dromaeosaurid showing transitional features.
- Published
- 2020
14. A large dromaeosaurid from North Carolina
- Author
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Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,food.ingredient ,biology ,Dakotaraptor ,Fauna ,Paleontology ,Vertebrate ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Cretaceous ,food ,Geography ,Group (stratigraphy) ,biology.animal ,Laramidia ,Appalachia ,Saurornitholestes ,0105 earth and related environmental sciences - Abstract
During the Cretaceous period, North America was divided into two landmasses, the eastern Appalachia and western Laramidia. Recent research on several sites scattered across the eastern margin of North America has allowed for the analysis of vertebrate faunas from the once obscure terrestrial fossil record of Appalachia, revealing the landmass harbored a distinctive fauna composed of mostly relict forms. One geological unit that has produced a comparatively extensive record of terrestrial vertebrates, including non-avian dinosaurs, is the middle Campanian Tar Heel Formation of North Carolina. Here, the first definitive occurrence of a dromaeosaurid from the Tar Heel Formation is reported on the basis of a tooth from a fairly large member of that group. This tooth clusters with those of dromaeosaurine dromaeosaurids from the western United States and Canada in morphometric analysis, differing in morphology and size from other dromaeosaurid teeth from southeastern North America that have been assigned to saurornitholestines or considered indeterminate. The tooth described herein is intermediate in size between those of smaller dromaeosaurids like Saurornitholestes and gigantic forms like Dakotaraptor, filling the gap between larger- and smaller-bodied dromaeosaurids from the Late Cretaceous.
- Published
- 2018
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15. The distinctive theropod assemblage of the Ellisdale site of New Jersey and its implications for North American dinosaur ecology and evolution during the Cretaceous
- Author
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Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,geography ,geography.geographical_feature_category ,biology ,Coastal plain ,Biogeography ,Paleontology ,Vertebrate ,010603 evolutionary biology ,01 natural sciences ,Cretaceous ,Taxon ,biology.animal ,Assemblage (archaeology) ,Evolutionary ecology ,Appalachia ,0105 earth and related environmental sciences - Abstract
The Cretaceous landmass of Appalachia has preserved an understudied but nevertheless important record of dinosaurs that has recently come under some attention. In the past few years, the vertebrate faunas of several Appalachian sites have been described. One such locality, the Ellisdale site of the Cretaceous Marshalltown Formation of New Jersey, has produced hundreds of remains assignable to dinosaurs, including those of hadrosauroids of several size classes, indeterminate ornithopods, indeterminate theropods, the teeth, cranial, and appendicular elements of dromaeosaurids, ornithomimosaurians, and tyrannosauroids, and an extensive microvertebrate assemblage. The theropod dinosaur record of the Ellisdale site is currently the most extensive and diverse known from the Campanian of Appalachia. Study of the Ellisdale theropod specimens suggests that at least four or more non-avian theropod taxa are represented at the site, including tyrannosauroids, ornithomimosaurs, several different morphotypes of dromaeosaurids that are the first of that clade described from New Jersey, and indeterminate theropods. The specimens are important for increasing current knowledge about the theropod diversity of the Atlantic Coastal Plain (ACP) during the Campanian by representing the most speciose assemblage of the group during the time in the ACP as well as for shedding light on Appalachian dinosaur ecology and biogeography generally.
- Published
- 2018
- Full Text
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16. Rebuttal of McFeeters, Ryan and Cullen, 2018, ‘Positional variation in pedal unguals of North American ornithomimids (Dinosauria, Theropoda): A Response to Brownstein (2017)’
- Author
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Chase D. Brownstein
- Subjects
biology ,Ornithomimosauria ,Theropoda ,biology.organism_classification ,Cretaceous ,Paleontology ,Taxon ,Geography ,Variation (linguistics) ,lcsh:Paleontology ,lcsh:Zoology ,Assemblage (archaeology) ,lcsh:QL1-991 ,Dinosauria ,lcsh:QE701-760 ,Arundel Clay - Abstract
The Arundel Clay of Maryland is among the only Early Cretaceous terrestrial units known from eastern North America. Research on some theropod dinosaur bones from this layer has indicated the presence of two ornithomimosaur taxa in the assemblage. However, a recent paper discussed issues with the definite assignment of any of these unguals to Ornithomimosauria and suggested that morphological differences originally interpreted to be indicative of the presence of two ornithomimosaurs could be explained by positional variation. Here, I show that substantial evidence persists for the presence of two ornithomimosaurs in the Arundel Clay assemblage, even considering the recent description of positional variation in ornithomimosaur pedal unguals. Furthermore, the argument against the confident assignment of these unguals to ornithomimosaurs is shown to be based on oversimplified comparisons that do not take into account the combination of features in the Arundel specimens that allow for their assignment to that clade. Although several small points made in the initial paper describing the Arundel specimens are incorrect or unsubstantiated, the differences between the Maryland unguals are outside the spectrum of positional variation and are indicative of the presence of two ornithomimosaurs in the Arundel Clay assemblage.
- Published
- 2018
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17. A tyrannosauroid tibia from the Navesink Formation of New Jersey and its biogeographic and evolutionary implications for North American tyrannosauroids
- Author
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Chase D. Brownstein
- Subjects
0301 basic medicine ,010506 paleontology ,biology ,Dryptosaurus ,Paleontology ,Western Interior Seaway ,biology.organism_classification ,01 natural sciences ,Archaeology ,Cretaceous ,03 medical and health sciences ,030104 developmental biology ,Geography ,Bistahieversor ,Laramidia ,Eotyrannus ,Appalachia ,0105 earth and related environmental sciences ,Appalachiosaurus - Abstract
The sparse dinosaur record of eastern North America has rendered the dinosaurs of the Late Cretaceous landmass of Appalachia obscure. Appalachia may have been a refugium for dinosaur species that would be replaced on Appalachia's western contemporary, Laramidia, from which the former landmass was isolated by the Western Interior Seaway. Among the theropods of the landmass, Appalachian tyrannosaurs are only represented currently by the two valid taxa Dryptosaurus aquilunguis and Appalachiosaurus montgomeriensis, a distinct but indeterminate taxon from the Campanian of Delaware, and indeterminate skeletons and isolated elements. New Jersey in particular has rendered many bones assignable to tyrannosauroids, contributing much to the study of members of this clade from Appalachia. Here, the partial tibia of a tyrannosauroid is described from the Maastrichtian Navesink Formation of Monmouth County, New Jersey. The specimen, originally described by paleontologists Edward Drinker Cope and Joseph Leidy, is important for revealing further the theropod fauna of the Navesink Formation of New Jersey and being the second definite occurrence of a tyrannosauroid in eastern North America during the Maastrichtian, thus illuminating the group's ecology and biogeography during that stage of the Cretaceous. Phylogenetic analysis plots the Navesink specimen as the sister taxon to Bistahieversor in a larger polytomy of all tyrannosauroids more derived than Eotyrannus, suggesting that the Navesink bone may represent either another “intermediate”-grade tyrannosauroid from Appalachia or a relative of B. sealeyi that migrated to eastern North America after the regression of the Western Interior Seaway.
- Published
- 2018
- Full Text
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18. A Tyrannosauroid from the Lower Cenomanian of New Jersey and Its Evolutionary and Biogeographic Implications
- Author
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Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,biology ,Range (biology) ,Biogeography ,Plant Science ,Body size ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Cretaceous ,Paleontology ,Geography ,Period (geology) ,Animal Science and Zoology ,Cenomanian ,Appalachia ,Ecology, Evolution, Behavior and Systematics ,0105 earth and related environmental sciences ,Appalachiosaurus - Abstract
The Barremian through Turonian record of tyrannosauroids in North America is sparse, and neither the western nor eastern portions of the continent have produced substantial material of early tyrant dinosaurs. This is unfortunate, as the discovery and description of several new tyrannosauroid genera from this temporal interval in recent years has shown that this period of time was likely when the tyrannosauroids evolved many of the signature features of the large- bodied genera that famously roamed the planet during the latest Cretaceous. One particular trait of the younger tyrant dinosaur genera that seems to have evolved during the aforementioned temporal interval was that of large body size. Here, I describe the metatarsal II of an indeterminate tyrannosauroid from the Cenomanian Potomac Formation of New Jersey. The metatarsal II is significant for several reasons. It is the only definite occurrence of a tyrannosauroid in eastern North America (Appalachia) before the Coniacian and Santonian and indicates an animal in the size range of tyrannosauroids from the Santonian to Maastrichtian of the Cretaceous. The New Jersey specimen thus differs from other, mostly small and gracile, known tyrannosaur genera of the mid-Cretaceous, suggesting that the evolution of large size among tyrannosauroids was a complex process. The metatarsal has morphological affinities to the corresponding metatarsal II of Appalachiosaurus montgomeriensis, and along with the results of phylogenetic analysis this suggests that Late Cretaceous Appalachian tyrannosauroids were relict forms isolated on the landmass.
- Published
- 2018
- Full Text
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19. The biogeography and ecology of the Cretaceous non-avian dinosaurs of Appalachia
- Author
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Chase D. Brownstein
- Subjects
0301 basic medicine ,010506 paleontology ,Ecology ,Ecology (disciplines) ,Biogeography ,Oceanography ,01 natural sciences ,Cretaceous ,03 medical and health sciences ,030104 developmental biology ,Geography ,Paleoecology ,Appalachia ,0105 earth and related environmental sciences - Published
- 2018
- Full Text
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20. Halszkaraptor escuilliei and the evolution of the paravian bauplan
- Author
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Chase D. Brownstein
- Subjects
0106 biological sciences ,0301 basic medicine ,Lineage (evolution) ,lcsh:Medicine ,Unenlagiinae ,010603 evolutionary biology ,01 natural sciences ,Article ,03 medical and health sciences ,Dromaeosauridae ,biology.animal ,Clade ,lcsh:Science ,Evolution of birds ,Multidisciplinary ,biology ,Palaeontology ,lcsh:R ,Rostrum ,Vertebrate ,biology.organism_classification ,Phylogenetics ,030104 developmental biology ,Body plan ,Evolutionary biology ,lcsh:Q - Abstract
The evolution of birds from dinosaurs is a subject that has received great attention among vertebrate paleontologists. Nevertheless, the early evolution of the paravians, the group that contains birds and their closest non-avian dinosaur relatives, remains very poorly known. Even the most basal members of one paravian lineage, the Dromaeosauridae, already show a body plan that differs substantially from their closest non-paravian relatives. Recently, the dromaeosaurid Halszkaraptor escuilliei was described from the Cretaceous of Mongolia. Halszkaraptor possesses numerous unserrated premaxillary teeth, a platyrostral rostrum with a developed neurovascular system, an elongate neck, bizarrely-proportioned forearms, and a foreword-shifted center of mass, differing markedly from other paravians. A reevaluation of the anatomy, taphonomy, environmental setting, and phylogenetic position of H. escuilliei based on additional comparisons with other maniraptorans suggests that, rather than indicating it was a semiaquatic piscivore, the body plan of this dinosaur bears features widely distributed among maniraptorans and in some cases intermediate between the conditions in dromaeosaurids and related clades. I find no evidence for a semiaquatic lifestyle in Halszkaraptor. A phylogenetic reevaluation of Halszkaraptorinae places it as the sister clade to Unenlagiinae, indicating the bizarre features of unenlagiines previously interpreted as evidence of piscivory may also represent a mosaic of plesiomorphic, derived, and intermediate features. The anatomy of Halszkaraptor reveals that dromaeosaurids still possessed many features found in more basal maniraptoran and coelurosaur clades, including some that may have been tied to herbivory. Rather than being a semiaquatic piscavore, Halszkaraptor was a basal dromaeosaurid showing transitional features.
- Published
- 2019
21. New records of theropods from the latest Cretaceous of New Jersey and the Maastrichtian Appalachian fauna
- Author
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Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,Fauna ,appalachia ,010603 evolutionary biology ,01 natural sciences ,Paleontology ,stomatognathic system ,biology.animal ,lcsh:Science ,fauna ,0105 earth and related environmental sciences ,teeth ,Multidisciplinary ,Extinction ,biology ,dinosaur ,Vertebrate ,Biology (Whole Organism) ,Cretaceous ,tyrannosaur ,Geography ,lcsh:Q ,Appalachia ,Research Article ,cretaceous - Abstract
The faunal changes that occurred in the few million years before the Cretaceous–Palaeogene extinction are of much interest to vertebrate palaeontologists. Western North America preserves arguably the best fossil record from this time, whereas terrestrial vertebrate fossils from the eastern portion of the continent are usually limited to isolated, eroded postcranial remains. Examination of fragmentary specimens from the American east, which was isolated for the majority of the Cretaceous as the landmass Appalachia, is nonetheless important for better understanding dinosaur diversity at the end of the Mesozoic. Here, I report on two theropod teeth from the Mount Laurel Formation, a lower-middle Maastrichtian unit from northeastern North America. One of these preserves in detail the structure of the outer enamel and resembles the dentition of the tyrannosauroid Dryptosaurus aquilunguis among latest Cretaceous forms in being heavily mediolaterally compressed and showing many moderately developed enamel crenulations. Along with previously reported tyrannosauroid material from the Mt Laurel and overlying Cretaceous units, this fossil supports the presence of non-tyrannosaurid tyrannosauroids in the Campanian–Maastrichtian of eastern North America and provides evidence for the hypothesis that the area was still home to relictual vertebrates through the end of the Mesozoic. The other tooth is assignable to a dromaeosaurid and represents both the youngest occurrence of a non-avian maniraptoran in eastern North America and the first from the Maastrichtian reported east of the Mississippi. This tooth, which belonged to a 3–4 m dromaeosaurid based on size comparisons with the teeth of taxa for which skeletons are known, increases the diversity of the Maastrichtian dinosaur fauna of Appalachia. Along with previously reported dromaeosaurid teeth, the Mt Laurel specimen supports the presence of mid-sized to large dromaeosaurids in eastern North America throughout the Cretaceous.
- Published
- 2019
- Full Text
- View/download PDF
22. The Rise and Fall of the Dinosaurs: A New History of a Lost World.— By Stephen L. Brusatte
- Author
-
Chase D Brownstein
- Subjects
0106 biological sciences ,0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Genetics ,Ancient history ,Biology ,010603 evolutionary biology ,01 natural sciences ,Ecology, Evolution, Behavior and Systematics - Published
- 2018
- Full Text
- View/download PDF
23. Diversity of raptor dinosaurs in southeastern North America revealed by the first definite record from North Carolina
- Author
-
Chase D. Brownstein
- Subjects
Geography ,media_common.quotation_subject ,Mesozoic ,Archaeology ,Appalachia ,Diversity (politics) ,media_common - Abstract
During the Cretaceous period, North America was divided into two landmasses, the eastern Appalachia and western Laramidia. Recent research on several sites scattered across the eastern margin of North America has allowed for the analysis of vertebrate faunas from the once obscured terrestrial fossil record of Appalachia, revealing the landmass harbored a distinctive fauna composed of mostly relict forms. One geological unit that has produced a comparatively extensive record of terrestrial vertebrates, including non-avian dinosaurs, is the Tar Heel Formation of North Carolina. Here, I report the first definitive occurrence of a dromaeosaurid from the Tar Heel Formation in the form of a tooth from a fairly large member of that group. This tooth, like others previously discovered from the southeastern portion of North America, compares favorably with those of saurornitholestine dromaeosaurids from the western United States and Canada. The North Carolina tooth differs in morphology and size from previously reported southeastern North American dromaeosaurid teeth, but is still assignable to a saurornitholestine dromaeosaurid, evincing that the diversity of carnivorous bird-like dinosaurs in the southeastern part of North America during the Late Cretaceous may have been rather low. The tooth, which is intermediate in size between those of smaller dromaeosaurids like Saurornitholestes and gigantic forms like Dakotaraptor, helps fill the gap between larger- and smaller-bodied dromaeosaurids from the Late Cretaceous.
- Published
- 2018
- Full Text
- View/download PDF
24. Theropod hindlimbs with feeding and other traces reveal ecosystem dynamics in the Maastrichtian of eastern North America
- Author
-
Chase D. Brownstein
- Subjects
Geography ,Taphonomy ,Ecology ,Ecosystem dynamics ,Appalachia ,Cretaceous - Abstract
Direct documentation of the ecology of past life is often rare when the fossil record is comparatively poor, as in the case of the terrestrial fauna of the Maastrichtian of eastern North America. Here, I describe a femur and partial tibia shaft assignable to theropods from the Maastrichtian Big Brook locality of New Jersey. The former, identifiable to a previously undetected morphotype of large ornithomimosaur, bears several scrapes identifiable as the feeding traces of sharks, adding to the collection of terrestrial vertebrate remains bearing such marks from the state. The latter is littered with tooth marks and punctures from possibly multiple crocodyliform individuals, the first documented occurrence of such traces on dinosaur bone from the Maastrichtian of the Atlantic Coastal Plain. Additionally, its surface is dotted with likely traces of invertebrates, revealing a microcosm of biological interaction from the Maastrichtian New Jersey shoreline. Previously, the massive Campanian crocodylian taxon Deinosuchus rugosus and the slightly smaller Cenomanian-age Texas crocodyliform Deltasuchus motherali have been shown as important drivers of terrestrial vertebrate taphonomy in eastern North America. The report of crocodyliform bite marks on the ornithomimosaur metatarsal shaft in this manuscript reveals that crocodylians continued to play role in the taphonomy of large dinosaurs in eastern North America through the end of the Mesozoic. The preserved invertebrate traces add to the sparse record of their traces on dinosaur bone, and the presence of shark scrapes on the femur supports the “bloat-and-float” model of terrestrial vertebrate fossil deposition in eastern North America.
- Published
- 2018
- Full Text
- View/download PDF
25. Prootic anatomy of a juvenile tyrannosauroid from New Jersey and its implications for the morphology and evolution of the tyrannosauroid braincase
- Author
-
Chase D. Brownstein
- Subjects
Juvenile ,Morphology (biology) ,Anatomy ,Biology ,Theropoda ,biology.organism_classification ,Cretaceous - Abstract
Among the most recognizable theropods are the tyrannosauroids, a group of small to large carnivorous coelurosaurian dinosaurs that inhabited the majority of the northern hemisphere during the Cretaceous and came to dominate large predator niches in North American and Asian ecosystems by the end of the Mesozoic era. The clade is among the best-represented of dinosaur groups in the notoriously sparse fossil record of Appalachia, the Late Cretaceous landmass that occupied the eastern portion of North America after its formation from the transgression of the Western Interior Seaway. Here, the prootic of a juvenile tyrannosauroid collected from the middle-late Campanian Marshalltown Formation of the Atlantic Coastal Plain is described, remarkable for being the first concrete evidence of juvenile theropods in that plain during the time of the existence of Appalachia and the only portion of theropod braincase known from the landmass. Phylogenetic analysis recovers the specimen as an “intermediate” tyrannosauroid of similar grade to Dryptosaurus and Appalachiosaurus. Comparisons with the corresponding portions of other tyrannosauroid braincases suggest that the Ellisdale prootic is more similar to Turonian forms in morphology than to the derived tyrannosaurids of the Late Cretaceous, thus supporting the hypothesis that Appalachian tyrannosauroids and other vertebrates were relict forms surviving in isolation from their derived counterparts in Eurasia.
- Published
- 2018
- Full Text
- View/download PDF
26. Caesar’s Bestiary: using classical accounts to statistically map changes in the large mammal fauna of Germany during the Pleistocene and Holocene
- Author
-
Chase D. Brownstein
- Subjects
0106 biological sciences ,010506 paleontology ,Pleistocene ,Fauna ,Wildlife ,Bestiary ,010603 evolutionary biology ,01 natural sciences ,Archaeology ,Geography ,Megafauna ,Mammal ,General Agricultural and Biological Sciences ,Holocene ,0105 earth and related environmental sciences - Abstract
In De Bello Gallico, Gaius Julius Caesar describes the various campaigns waged by the Romans under his leadership against the ‘Gauls’ and the geography, wildlife, and the various tribes of the lands he observed during his time in ‘Gallia’. Caesar remarks in one passage in chapters 26–28 of book 6 on the large mammals of an area of wilderness known to him as ‘Hercynia Silva,’ the Hercynian Forest. This passage, analyzed previously by several authors who identified the animals Caesar described and compared his descriptions with those of several mythological creatures, allows for a unique glimpse into the large mammal fauna of Germany of ~ 2000 years ago, as the mammals Caesar mentions include several species either locally extirpated from Germany or extinct altogether. Here, I review these descriptions and prior analyses of their meaning to compile a faunal list of the Hercynian forest megafauna from the Classical period. Additionally, I briefly statistically compare this faunal to several from Pleistocene Germany. These comparisons serve to both demonstrate changes in the megafauna of Europe during the late Quaternary and the use of classical sources in paleobiogeography and paleoecology.
- Published
- 2018
- Full Text
- View/download PDF
27. Description of Arundel Clay ornithomimosaur material and a reinterpretation of Nedcolbertia justinhofmanni as an 'Ostrich Dinosaur': biogeographic implications
- Author
-
Chase D. Brownstein
- Subjects
010506 paleontology ,Potomac group ,Biogeography ,Fauna ,lcsh:Medicine ,Stratigraphic unit ,Early Cretaceous ,Arundel formation ,010502 geochemistry & geophysics ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Paleontology ,Arundel Formation ,Ornithomimosaurs ,0105 earth and related environmental sciences ,Potomac Group ,biology ,Maryland ,Theropods ,General Neuroscience ,lcsh:R ,Nedcolbertia ,General Medicine ,biology.organism_classification ,Cretaceous ,Geography ,Taxon ,General Agricultural and Biological Sciences - Abstract
The fossil record of dinosaurs from the Early Cretaceous of Eastern North America is scant, especially since a few stratigraphic units from the east are fossiliferous. Among these stratigraphic units, the Arundel Clay of the eastern seaboard has produced the best-characterized dinosaur faunas known from the Early Cretaceous of Eastern North America. The diverse dinosaur fauna of the Arundel Clay has been thoroughly discussed previously, but a few of the dinosaur species originally described from the Arundel Clay are still regarded as valid genera. Much of the Arundel material is in need of review and redescription. Among the fossils of dinosaurs from this stratigraphic unit are those referred to ornithomimosaurs. Here, the researcher describes ornithomimosaur remains from the Arundel Clay of Prince George’s County, Maryland which may be from two distinct ornithomimosaur taxa. These remains provide key information on the theropods of the Early Cretaceous of Eastern North America. Recent discoveries of small theropod material from the Arundel Clay possibly belonging to ornithomimosaurs are also reviewed and described for the first time. The description of the Arundel material herein along with recent discoveries of basal ornithomimosaurs in the past 15 years has allowed for comparisons with the coelurosaurNedcolbertia justinhofmanni, suggesting the latter animal was a basal ornithomimosaur rather than a “generalized” coelurosaur as it was originally described. Comparisons between the Arundel ornithomimosaur material and similar Asian and European specimens suggest that both extremely basal ornithomimosaurs and more intermediate or derived forms may have coexisted throughout the northern hemisphere during the Early Cretaceous.
- Published
- 2017
28. First Record of a Small Juvenile Giant Crocodyliform and its Ontogenetic and Biogeographic Implications
- Author
-
Chase D. Brownstein
- Subjects
0106 biological sciences ,Deinosuchus ,010506 paleontology ,Dentition ,biology ,Biogeography ,Zoology ,Plant Science ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Cretaceous ,Taxon ,Genus ,Juvenile ,Animal Science and Zoology ,Predator ,Ecology, Evolution, Behavior and Systematics ,0105 earth and related environmental sciences - Abstract
Deinosuchus is a genus of large crocodylian that inhabited North America during the Late Cretaceous. This massive predator has become one of the most well-known prehistoric organisms, with a considerable amount of literature on its biogeography, ecology, and evolution published. However, ontogenetic changes of Deinosuchus and other species of extinct large, predatory crocodyliforms have remained poorly understood because of a lack of remains known from juvenile individuals and issues surrounding the ability of histological analysis of adult material to provide information on yearly growth. Here, I describe a tooth from a juvenile Deinosuchus estimated at less than 1m in total body length. As the first reported specimen of a juvenile Deinosuchus, to the author's knowledge, in the literature, the new fossil evinces the extremely small size of young individuals of this taxon compared to adults more than 8 m and 3,500 kg. Furthermore, the tooth shows that some morphological discrepancies existed between the dentition of juvenile and adult Deinosuchus individuals, including the size of the nutritive region. In addition to being the first specimen of Deinosuchus from northeastern North America described in detail, the tooth emphasizes the biological extremes of attaining large body size in Deinosuchus and may add support to the hypothesis that the ontogeny of gigantic crocodyliforms was characterized by extended periods of juvenile growth.
- Published
- 2019
- Full Text
- View/download PDF
29. The northernmost occurrence of Chelydra serpentina in the eastern US during the Pleistocene
- Author
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Chase D. Brownstein
- Subjects
geography ,Taphonomy ,geography.geographical_feature_category ,biology ,Pleistocene ,Range (biology) ,biology.organism_classification ,Cretaceous ,law.invention ,Paleontology ,law ,Macrochelys ,Turtle (robot) ,Ice sheet ,Chelydra ,Geology - Abstract
The snapping turtle species Chelydra serpentina, which has a wide range across North America, is extremely tolerant to cold and even freezing conditions. Here, I describe a single caudal vertebrae referred to Chelydra serpentina from the Late Pleistocene of New Jersey which represents the northernmost known occurrence of the species in eastern North America and the closest known occurrence of the species to a glacier or ice sheet in the continent during the Pleistocene. The specimen, which was collected at Ramanessin Brook in Holmdel, New Jersey, affirms that the Pleistocene deposits which line the banks of the popular Cretaceous site are not taphonomically biased to preserving larger fossils and in the future may yield an assemblage of small vertebrates. Introduction. The chelydrids, more commonly known as snapping turtles, are a family of large freshwater turtles that are represented presently by the two genera Chelydra and Macrochelys. The first appearance of this turtle family comes from the Late Cretaceous of Montana (Whetstone, 1978), and extinct species are known from Asia, Europe, and North America (e.g. Pidoplichko & Tarashchuk, 1960; Klein & Mors, 2003; Danilov & Parham, 2008).
- Published
- 2016
- Full Text
- View/download PDF
30. Characterisation of organisational issues in paediatric clinical ethics consultation: a qualitative study
- Author
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Robert A. Pearlman, Benjamin S. Wilfond, Douglas S. Diekema, D Brownstein, and Douglas J. Opel
- Subjects
Washington ,medicine.medical_specialty ,Health (social science) ,Quality management ,Knowledge management ,Adolescent ,Organizational culture ,Pediatrics ,Arts and Humanities (miscellaneous) ,Information ethics ,medicine ,Humans ,Organizational Objectives ,Child ,Qualitative Research ,Ethics Consultation ,Upstream (petroleum industry) ,Nursing ethics ,business.industry ,Health Policy ,Infant, Newborn ,Infant ,Public relations ,Organizational Culture ,Organizational Policy ,Issues, ethics and legal aspects ,Ethics, Clinical ,Content analysis ,Child, Preschool ,business ,Qualitative research - Abstract
Background: The traditional approach to resolving ethics concerns may not address underlying organisational issues involved in the evolution of these concerns. This represents a missed opportunity to improve quality of care “upstream”. The purpose of this study was to understand better which organisational issues may contribute to ethics concerns. Methods: Directed content analysis was used to review ethics consultation notes from an academic children’s hospital from 1996 to 2006 (N = 71). The analysis utilised 18 categories of organisational issues derived and modified from published quality improvement protocols. Results: Organisational issues were identified in 68 of the 71 (96%) ethics consult notes across a range of patient settings and reasons for consultation. Thirteen of the 18 categories of organisational issues were identified and there was a median of two organisational issues per consult note. The most frequently identified organisational issues were informal organisational culture (eg, collective practices and approaches to situations with ethical dimensions that are not guided by policy), policies and procedures (eg, staff knows policy and/or procedural guidelines for an ethical concern but do not follow it) and communication (eg, communication about critical information, orders, or hand-offs repeatedly does not occur among services). Conclusions: Organisational issues contribute to ethical concerns that result in clinical ethics consults. Identifying and addressing organisational issues such as informal culture and communication may help decrease the recurrence of future similar ethics concerns.
- Published
- 2009
- Full Text
- View/download PDF
31. Severe osteochondrosis in two 10-month-old beef calves
- Author
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Phil Scott, Susan Rhind, and D. Brownstein
- Subjects
Male ,Veterinary medicine ,General Veterinary ,business.industry ,Lameness, Animal ,Cattle Diseases ,General Medicine ,medicine.disease ,Diagnosis, Differential ,Animals, Newborn ,Osteochondrosis ,Medicine ,Animals ,Cattle ,Female ,business ,Osteochondritis - Published
- 2000
32. Diabetes mellitus associated with lymphocytic islet inflammation in a Charolais bull
- Author
-
Phil Scott, Colin Penny, D. Brownstein, and Karin Mueller
- Subjects
Male ,medicine.medical_specialty ,Fever ,Cattle Diseases ,Enzyme-Linked Immunosorbent Assay ,Inflammation ,Lymphocytosis ,Diabetes Complications ,Islets of Langerhans ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Animals ,geography ,Diarrhea Viruses, Bovine Viral ,geography.geographical_feature_category ,General Veterinary ,business.industry ,General Medicine ,Islet ,medicine.disease ,Endocrinology ,Cattle ,medicine.symptom ,business - Published
- 2001
- Full Text
- View/download PDF
33. Fluorescence studies on the active sites of porcine pepsin and Rhizopus-pepsin
- Author
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Allen D. Brownstein, Goverdhan P. Sachdev, and Joseph S. Fruton
- Subjects
chemistry.chemical_classification ,Oligopeptide ,animal structures ,integumentary system ,biology ,Chemistry ,Active site ,Peptide ,Cell Biology ,biology.organism_classification ,Biochemistry ,Fluorescence ,Porcine pepsin ,chemistry.chemical_compound ,Pepsin ,Rhizopus ,biology.protein ,Molecular Biology ,Pepstatin - Abstract
Fluorescence studies on the interaction, with porcine pepsin, of oligopeptides bearing a mansyl (Mns, 6-(N-methylanilino)-2-naphthalenesulfonyl) or dansyl (Dns, 5-dimethylaminonaphthalene-1-sulfonyl) group at the NH2 or COOH terminus have provided further evidence showing that the probe group is drawn into the extended active site largely as a consequence of the specific binding of the peptide portion of the substrate. The active site does not appear to have appreciable intrinsic affinity for the mansyl or dansyl group, and the principal contribution to the specific peptide-protein interaction is provided by the sensitive L-phenylalanyl-L-phenylalanyl (Phe-Phe) unit of the substrates tested. The pepsin inhibitor pepstatin can displace substrates such as Mns-(Gly)n-Phe-Phe-OR or Gly-Gly-Phe-Phe-NHNH-Mns from the active site of porcine pepsin; in these circumstances the mansyl group is bound weakly at a separate, nonspecific locus, distinct from the active site, which can accept the mansyl group of Mns-Gly-Gly-OR or mansylamide. In the interaction with substrates such as Mns-(Gly)n-Phe-Phe-OR or Dns-(Gly)n-Phe-Phe-OR, the above conclusions for porcine pepsin also apply to Rhizopus-pepsin. With substrates such as Gly-Gly-Phe-Phe-NHNH-Mns, however, the active site of Rhizopus-pepsin shows less affinity for the fluorescent probe group than does that of porcine pepsin, suggesting structural differences between the two acid proteinases in the region of their extended active sites which bind the COOH-terminal portion of small oligopeptide substrates.
- Published
- 1975
- Full Text
- View/download PDF
34. Interaction of 9-Peptidylaminoacridines with Proteins and Nucleic Acids
- Author
-
Allen D. Brownstein, Goverdhan P. Sachdev, and Joseph S. Fruton
- Subjects
chemistry.chemical_classification ,biology ,Serum albumin ,Active site ,Cell Biology ,Biochemistry ,chemistry.chemical_compound ,Enzyme ,chemistry ,Polynucleotide ,Acridine ,Nucleic acid ,biology.protein ,Bovine serum albumin ,Lysozyme ,Molecular Biology - Abstract
Several 9-peptidylaminoacridines have been synthesized, their spectroscopic properties have been examined, and studies have been performed by means of absorption and fluorescence spectrophotometry on their interaction with proteins (especially pepsin) and with DNA preparations. At pH 5, pepsin binds 9-(Phe-Phe-amino) acridine largely by virtue of the interaction of the Phe-Phe unit of the compound with the extended active site of the enzyme, the acridine portion being drawn into a region of lower polarity than that of the aqueous medium. The results obtained with pepsin are compared with those given by bovine serum albumin, α-chymotrypsin, and lysozyme. Although, at pH 5, 9-(Phe-Phe-amino)acridine appears to be bound by DNA preparations somewhat more tightly than is 9-acetylaminoacridine, the absorption and emission spectra of these acyl-aminoacridines are not altered by interaction with DNA to the extent seen with the 9-aminoacridinium cation under comparable experimental conditions.
- Published
- 1974
- Full Text
- View/download PDF
35. N-Methyl-2-anilinonaphthalene-6-sulfonyl Peptides as Fluorescent Probes for Pepsin-Substrate Interaction
- Author
-
Joseph S. Fruton, Allen D. Brownstein, and Goverdhan P. Sachdev
- Subjects
chemistry.chemical_classification ,Oligopeptide ,biology ,Active site ,Peptide ,Cell Biology ,Biochemistry ,Fluorescence ,chemistry.chemical_compound ,Enzyme ,chemistry ,Pepsin ,biology.protein ,Biophysics ,Binding site ,Molecular Biology ,Pepstatin - Abstract
Advantage has been taken of the high sensitivity of the N-methyl-2-anilinonaphthalene-6-sulfonyl (mansyl) group as a fluorescent probe for hydrophobic regions of proteins to study the interaction of pepsin with mansylamide and with several peptides bearing an amino-terminal mansyl group. The data indicate that pepsin has a binding site for mansylamide that is distinct from the substrate-binding region of the enzyme. When a mansyl group is attached to a peptide having an l-phenylalanyl-l-phenylalanyl bond, previously identified as a preferred linkage for attack by pepsin, the fluorescent probe appears to be drawn into a hydrophobic region not evident in the interaction with mansylamide. Upon the addition of pepstatin, a powerful competitive inhibitor of pepsin, the enhancement of the fluorescence of mansylamide is unaffected, but that of the mansyl peptides is reduced to the value for mansylamide. Further evidence for the discrete nature of the binding sites in pepsin for mansylamide and for the mansyl group of peptide substrates is provided by the fact that, upon autocatalytic activation of pepsinogen, the enhancement of the fluorescence of mansylamide is decreased, whereas that of the mansyl peptides is increased; both effects are abolished by pepstatin. Studies on the fluorescence of mansylamide and of mansyl peptides in the presence of pepsin that had been stoichiometrically inactivated by treatment with tosyl-l-phenyl-alanyldiazomethane have shown that this active site-directed inhibitor not only blocks the access of a mansyl peptide substrate to the active site, but also alters the mansylamide-binding site so as to lower its polarity. Further evidence for the conformational flexibility of pepsin suggested by this finding is provided by data on the partially acetylated enzyme, which is more active toward oligopeptide substrates than is pepsin itself. With acetyl-pepsin, the enhancement of the fluorescence of mansyl peptides (but not of mansylamide) is much greater than with untreated pepsin. The addition of pepstatin, however, markedly alters the polarity of the mansylamide-binding site of acetyl-pepsin. Data are presented for the kinetics of the cleavage, by pepsin, of several mansyl peptide substrates. These results, together with those from the fluorescence studies, give further evidence of the importance of secondary interactions of pepsin substrates with the extended active site of the enzyme in influencing catalytic efficiency without marked change in total binding energy. It is difficult to accommodate the findings reported here with a relatively rigid extended active site that can be mapped in terms of subsites; instead, pepsin appears to exhibit considerable conformational flexibility at the active site in response to enzyme-substrate (or enzyme-inhibitor) interaction.
- Published
- 1973
- Full Text
- View/download PDF
36. Duration and patterns of transmission of Theiler's mouse encephalomyelitis virus infection
- Author
-
D, Brownstein, P, Bhatt, R, Ardito, F, Paturzo, and E, Johnson
- Subjects
Rodent Diseases ,Maus Elberfeld virus ,Mice ,Time Factors ,Hydrocortisone ,Enterovirus Infections ,Animals ,Female ,Antibodies, Viral ,Cyclophosphamide ,Housing, Animal - Abstract
The duration and patterns of Theiler's murine encephalomyelitis virus (TMEV) transmission were studied in eight index mice inoculated orally. Transmission was monitored by testing for seroconversion to TMEV in sentinel mice in direct contact with index mice and in other sentinel mice in contact with bedding soiled by index mice. For the first 14 weeks after inoculation, two contact sentinels were housed with each index mouse for 1 week, then replaced with two new sentinels. For the remaining 16 weeks, contact sentinels were changed monthly. All index mice transmitted TMEV continuously (weekly) for 4 to 9 weeks. Thereafter, six index mice transmitted virus intermittently. All index mice ceased transmitting TMEV 7 to 22 weeks post-inoculation. Results obtained from sentinel mice in contact with bedding soiled by index mice were 86% concordant with those using contact sentinel mice. Seven index mice were treated with cyclophosphamide or hydrocortisone 30 weeks post-inoculation. One cyclophosphamide treated mouse reinitiated virus shedding.
- Published
- 1989
37. Vaccine-induced canine distemper in a lesser panda
- Author
-
M, Bush, R J, Montali, D, Brownstein, A E, James, and M J, Appel
- Subjects
Male ,Dogs ,Carnivora ,Animals ,Animals, Zoo ,Viral Vaccines ,Distemper ,Distemper Virus, Canine ,Lung - Abstract
A fatal disease occurred in a lesser panda (Ailurus fulgens) 2 weeks after vaccination with modified live distemper vaccine. The disease clinically resembled canine distemper. Pathologically there was giant cell pneumonia, with canine distemper viral inclusion bodies in pulmonary and digestive tract epithelium. Viral isolates were indicative of an attenuated strain rather than virulent types.
- Published
- 1976
38. Fluorescence studies on the active sites of porcine pepsin and Rhizopus-pepsin
- Author
-
G P, Sachdev, A D, Brownstein, and J S, Fruton
- Subjects
Dansyl Compounds ,Kinetics ,Structure-Activity Relationship ,Binding Sites ,Spectrometry, Fluorescence ,Protein Conformation ,Swine ,Animals ,Anilino Naphthalenesulfonates ,Pepsin A ,Rhizopus ,Protein Binding - Abstract
Fluorescence studies on the interaction, with porcine pepsin, of oligopeptides bearing a mansyl (Mns, 6-(N-methylanilino)-2-naphthalenesulfonyl) or dansyl (Dns, 5-dimethylaminonaphthalene-1-sulfonyl) group at the NH2 or COOH terminus have provided further evidence showing that the probe group is drawn into the extended active site largely as a consequence of the specific binding of the peptide portion of the substrate. The active site does not appear to have appreciable intrinsic affinity for the mansyl or dansyl group, and the principal contribution to the specific peptide-protein interaction is provided by the sensitive L-phenylalanyl-L-phenylalanyl (Phe-Phe) unit of the substrates tested. The pepsin inhibitor pepstatin can displace substrates such as Mns-(Gly)n-Phe-Phe-OR or Gly-Gly-Phe-Phe-NHNH-Mns from the active site of porcine pepsin; in these circumstances the mansyl group is bound weakly at a separate, nonspecific locus, distinct from the active site, which can accept the mansyl group of Mns-Gly-Gly-OR or mansylamide. In the interaction with substrates such as Mns-(Gly)n-Phe-Phe-OR or Dns-(Gly)n-Phe-Phe-OR, the above conclusions for porcine pepsin also apply to Rhizopus-pepsin. With substrates such as Gly-Gly-Phe-Phe-NHNH-Mns, however, the active site of Rhizopus-pepsin shows less affinity for the fluorescent probe group than does that of porcine pepsin, suggesting structural differences between the two acid proteinases in the region of their extended active sites which bind the COOH-terminal portion of small oligopeptide substrates.
- Published
- 1975
39. ChemInform Abstract: The Azomethine Imine Route to Guanidines. Total Synthesis of (±)-Saxitoxin
- Author
-
S. Polanc, Peter A. Jacobi, A. D. Brownstein, and Michael John Martinelli
- Subjects
Saxitoxin ,chemistry.chemical_compound ,chemistry ,Imine ,Organic chemistry ,Total synthesis ,General Medicine - Published
- 1986
- Full Text
- View/download PDF
40. The Azomethine Imine Route to Guanidines. Total Synthesis of (+)-Saxitoxin
- Author
-
Michael J. Martinelli, Allen D. Brownstein, Peter A. Jacobi, Slovenka Polanc, Michael J. Martinelli, Allen D. Brownstein, Peter A. Jacobi, and Slovenka Polanc
- Abstract
Azomethine imines may be readily generated through the interaction of aldehyde aeetals with earboxylie acid hydrazides. These reaetions are most highly favored in pollar aprotie solvents and aeid eatalysis is required. With suitably funetionalized hydrazides these substanees undergo a faeile intramolecular addition to give fused-ring pyrazolidine derivati ves. As a part of these studies, (± )-Saxitoxin (7), the paralytie agent of the Alaska butter elam Saxidomas giganteus, has been synthesized in a totally stereospecific fashion through a sequenee involving as the key steps: (a) intramolecular 1,3-dipolar addition of an azomethine imine to a 2-imidazolone; (b) reductive cleavage of the resulting pyrazolidine ring followed by intramoleeular acylation; and (c) final elaboration of a bis-pseudourea to the requisite guanidine functionality.
- Published
- 1986
41. N-methyl-2-anilinonaphthalene-6-sulfonyl peptides as fluorescent probes for pepsin-substrate interaction
- Author
-
G P, Sachdev, A D, Brownstein, and J S, Fruton
- Subjects
Chromatography ,Aniline Compounds ,Binding Sites ,Time Factors ,Chromatography, Paper ,Naphthalenes ,Silicon Dioxide ,Fluorescence ,Pepsin A ,Kinetics ,Spectrometry, Fluorescence ,Spectrophotometry, Ultraviolet ,Sulfonic Acids ,Peptides ,Protein Binding - Published
- 1973
42. Interaction of 9-peptidylaminoacridines with proteins and nucleic acids
- Author
-
G P, Sachdev, A D, Brownstein, and J S, Fruton
- Subjects
Binding Sites ,Pepsinogens ,Phenylalanine ,Polynucleotides ,Serum Albumin, Bovine ,DNA ,Thymus Gland ,Fluorescence ,Pepsin A ,Kinetics ,Structure-Activity Relationship ,Spectrometry, Fluorescence ,Salmon ,Spectrophotometry ,Acridines ,Animals ,Chymotrypsin ,Cattle ,Muramidase ,Spectrophotometry, Ultraviolet ,Amines ,Peptides ,Oligopeptides - Published
- 1974
43. Iodide Transporters in the Endometrium: A Potential Diagnostic Marker for Women with Recurrent Pregnancy Failures.
- Author
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Bilal MY, Dambaeva S, Brownstein D, Kwak-Kim J, Gilman-Sachs A, and Beaman KD
- Subjects
- Adult, Biomarkers, Embryo Transfer, Female, Humans, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sulfate Transporters biosynthesis, Symporters biosynthesis, Thyroglobulin biosynthesis, Abortion, Spontaneous physiopathology, Endometrium cytology, Iodine metabolism, Membrane Transport Proteins biosynthesis
- Abstract
Objective: The element iodine is an essential nutrient utilized by the thyroid glands, and deficiency of this element has been linked to reproductive failures. Iodide transporters are also present in reproductive tissues and cells of embryonic origin such as the endometrium and trophoblasts, respectively. The aim of this study is to understand if levels of iodide transporters are linked to pregnancy outcomes., Subjects and Methods: RNA derived from endometrial biopsies from controls or women with recurrent reproductive failures was analyzed utilizing RT-PCR and targeted RNASeq., Results: When compared to controls, women with 2 or more reproductive failures had a significant increase (>5 fold) in mRNA levels of the iodine transporters NIS and PENDRIN, but not thyroglobulin when probed vis RT-PCR. Targeted RNASeq analysis confirmed these findings when another group of patients were analyzed., Conclusion: These findings suggest possible abnormal iodine metabolism and a deficiency of iodine in endometrial tissues from some of the women with reproductive failures. We hypothesize from these findings that inorganic iodide and/or iodine is required for optimal cellular function in reproductive tissues, and that iodide transporters may potentially be used as a marker for infertility or for probing potential localized iodine deficiency that may not present in a typical thyroid panel analysis., (© 2020 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2020
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44. Deducing the stage of origin of Wilms' tumours from a developmental series of Wt1-mutant mice.
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Berry RL, Ozdemir DD, Aronow B, Lindström NO, Dudnakova T, Thornburn A, Perry P, Baldock R, Armit C, Joshi A, Jeanpierre C, Shan J, Vainio S, Baily J, Brownstein D, Davies J, Hastie ND, and Hohenstein P
- Subjects
- Animals, Biomarkers metabolism, Cell Lineage, Gene Expression Regulation, Neoplastic, Genome, Integrases metabolism, Mice, Inbred C57BL, Mice, Mutant Strains, Neoplasm Staging, Nephrons pathology, Oligonucleotide Array Sequence Analysis, Phenotype, Time-Lapse Imaging, WT1 Proteins genetics, Wilms Tumor genetics, Nephrons growth & development, Nephrons metabolism, WT1 Proteins metabolism, Wilms Tumor pathology
- Abstract
Wilms' tumours, paediatric kidney cancers, are the archetypal example of tumours caused through the disruption of normal development. The genetically best-defined subgroup of Wilms' tumours is the group caused by biallelic loss of the WT1 tumour suppressor gene. Here, we describe a developmental series of mouse models with conditional loss of Wt1 in different stages of nephron development before and after the mesenchymal-to-epithelial transition (MET). We demonstrate that Wt1 is essential for normal development at all kidney developmental stages under study. Comparison of genome-wide expression data from the mutant mouse models with human tumour material of mutant or wild-type WT1 datasets identified the stage of origin of human WT1-mutant tumours, and emphasizes fundamental differences between the two human tumour groups due to different developmental stages of origin., (© 2015. Published by The Company of Biologists Ltd.)
- Published
- 2015
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45. A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton.
- Author
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Carpanini SM, McKie L, Thomson D, Wright AK, Gordon SL, Roche SL, Handley MT, Morrison H, Brownstein D, Wishart TM, Cousin MA, Gillingwater TH, Aligianis IA, and Jackson IJ
- Subjects
- Animals, Cataract physiopathology, Cornea physiopathology, Mice, Mice, Knockout, rab GTP-Binding Proteins genetics, Abnormalities, Multiple physiopathology, Cataract congenital, Cornea abnormalities, Cytoskeleton physiology, Disease Models, Animal, Eye growth & development, Hypogonadism physiopathology, Intellectual Disability physiopathology, Microcephaly physiopathology, Neurons physiology, Optic Atrophy physiopathology, rab GTP-Binding Proteins physiology
- Abstract
Mutations in RAB18 have been shown to cause the heterogeneous autosomal recessive disorder Warburg Micro syndrome (WARBM). Individuals with WARBM present with a range of clinical symptoms, including ocular and neurological abnormalities. However, the underlying cellular and molecular pathogenesis of the disorder remains unclear, largely owing to the lack of any robust animal models that phenocopy both the ocular and neurological features of the disease. We report here the generation and characterisation of a novel Rab18-mutant mouse model of WARBM. Rab18-mutant mice are viable and fertile. They present with congenital nuclear cataracts and atonic pupils, recapitulating the characteristic ocular features that are associated with WARBM. Additionally, Rab18-mutant cells exhibit an increase in lipid droplet size following treatment with oleic acid. Lipid droplet abnormalities are a characteristic feature of cells taken from WARBM individuals, as well as cells taken from individuals with other neurodegenerative conditions. Neurological dysfunction is also apparent in Rab18-mutant mice, including progressive weakness of the hind limbs. We show that the neurological defects are, most likely, not caused by gross perturbations in synaptic vesicle recycling in the central or peripheral nervous system. Rather, loss of Rab18 is associated with widespread disruption of the neuronal cytoskeleton, including abnormal accumulations of neurofilament and microtubule proteins in synaptic terminals, and gross disorganisation of the cytoskeleton in peripheral nerves. Global proteomic profiling of peripheral nerves in Rab18-mutant mice reveals significant alterations in several core molecular pathways that regulate cytoskeletal dynamics in neurons. The apparent similarities between the WARBM phenotype and the phenotype that we describe here indicate that the Rab18-mutant mouse provides an important platform for investigation of the disease pathogenesis and therapeutic interventions., (© 2014. Published by The Company of Biologists Ltd.)
- Published
- 2014
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46. In vivo characterization of the role of tissue-specific translation elongation factor 1A2 in protein synthesis reveals insights into muscle atrophy.
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Doig J, Griffiths LA, Peberdy D, Dharmasaroja P, Vera M, Davies FJ, Newbery HJ, Brownstein D, and Abbott CM
- Subjects
- Animals, Gene Expression Regulation, Mice, Mice, Knockout, Muscle Proteins biosynthesis, Muscle, Skeletal pathology, Muscular Atrophy metabolism, Muscular Atrophy pathology, Neurodegenerative Diseases genetics, Neurons metabolism, Organ Specificity, Peptide Elongation Factor 1 metabolism, SKP Cullin F-Box Protein Ligases biosynthesis, Up-Regulation, Muscular Atrophy genetics, Neurons pathology, Peptide Chain Elongation, Translational genetics, Peptide Elongation Factor 1 genetics
- Abstract
Translation elongation factor 1A2 (eEF1A2), uniquely among translation factors, is expressed specifically in neurons and muscle. eEF1A2-null mutant wasted mice develop an aggressive, early-onset form of neurodegeneration, but it is unknown whether the wasting results from denervation of the muscles, or whether the mice have a primary myopathy resulting from loss of translation activity in muscle. We set out to establish the relative contributions of loss of eEF1A2 in the different tissues to this postnatal lethal phenotype. We used tissue-specific transgenesis to show that correction of eEF1A2 levels in muscle fails to ameliorate the overt phenotypic abnormalities or time of death of wasted mice. Molecular markers of muscle atrophy such as Fbxo32 were dramatically upregulated at the RNA level in wasted mice, both in the presence and in the absence of muscle-specific expression of eEF1A2, but the degree of upregulation at the protein level was significantly lower in those wasted mice without transgene-derived expression of eEF1A2 in muscle. This provides the first in vivo confirmation that eEF1A2 plays an important role in translation. In spite of the inability of the nontransgenic wasted mice to upregulate key atrogenes at the protein level in response to denervation to the same degree as their transgenic counterparts, there were no measurable differences between transgenic and nontransgenic wasted mice in terms of weight loss, grip strength, or muscle pathology. This suggests that a compromised ability fully to execute the atrogene pathway in denervated muscle does not affect the process of muscle atrophy in the short term., (© 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of FEBS.)
- Published
- 2013
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47. Association between language, serious adverse events, and length of stay among hospitalized children.
- Author
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Lion KC, Rafton SA, Shafii J, Brownstein D, Michel E, Tolman M, and Ebel BE
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Female, Hospitals, Pediatric, Humans, Infant, Male, Odds Ratio, Retrospective Studies, Communication Barriers, Hispanic or Latino statistics & numerical data, Language, Length of Stay statistics & numerical data, Medical Errors statistics & numerical data, White People statistics & numerical data
- Abstract
Objective: To evaluate the risk for serious/sentinel adverse events among hospitalized children according to race, ethnicity, and language and to evaluate factors affecting length of stay associated with serious/sentinel adverse events., Methods: We conducted a retrospective cohort study of all pediatric inpatients at a large children's hospital from October 2007 to October 2009. We evaluated the relationship between self-reported race, ethnicity, and primary language; with having a serious or sentinel adverse event, defined as an unexpected occurrence involving risk of death or serious injury; or a potentially harmful event resulting from nonstandard practice. We also examined length of stay. Clinical complexity was adjusted for by using Clinical Risk Groups., Results: Of 33885 patients, 8% spoke Spanish and 4% spoke other languages. Serious and sentinel events were rare; however, among patients with such events, 14% spoke Spanish. Adjusting for potential confounders, Spanish speakers trended toward an elevated odds of adverse event (odds ratio: 1.83 [95% confidence interval: 0.98-3.39]). Controlling for age, language, and clinical complexity, having an adverse event was associated with a nearly fivefold increase in length of stay (95% confidence interval: 3.87-6.12). Spanish-speaking patients with an adverse event were hospitalized significantly longer than comparable English speakers (26 vs 12.7 days; P = .03 for interaction between language and adverse event)., Conclusions: Hospitalized children from Spanish-speaking families had significantly longer hospital stays in association with an adverse event and may have increased odds of a serious or sentinel event. These findings suggest that an important component of patient safety may be to address communication barriers.
- Published
- 2013
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48. Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1.
- Author
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Chau YY, Brownstein D, Mjoseng H, Lee WC, Buza-Vidas N, Nerlov C, Jacobsen SE, Perry P, Berry R, Thornburn A, Sexton D, Morton N, Hohenstein P, Freyer E, Samuel K, van't Hof R, and Hastie N
- Subjects
- Animals, Atrophy genetics, Atrophy pathology, Cell Lineage genetics, Epithelial-Mesenchymal Transition genetics, Female, Gene Deletion, Gene Expression Regulation, Glomerulonephritis pathology, Gonads embryology, Gonads metabolism, Gonads pathology, Hematopoiesis genetics, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Kidney Glomerulus embryology, Kidney Glomerulus metabolism, Kidney Glomerulus pathology, Male, Membrane Proteins genetics, Membrane Proteins metabolism, Mesenchymal Stem Cells metabolism, Mice, Mice, Transgenic, Multiple Organ Failure pathology, Pancreas, Exocrine embryology, Pancreas, Exocrine metabolism, Pancreas, Exocrine pathology, Podocytes metabolism, Podocytes pathology, Spleen embryology, Spleen metabolism, Spleen pathology, Tamoxifen pharmacology, WT1 Proteins genetics, Glomerulonephritis genetics, Homeostasis genetics, Multiple Organ Failure genetics, WT1 Proteins physiology
- Abstract
There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal-epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors. Although Wt1 is only expressed in rare cell populations in adults including glomerular podocytes, 1% of bone marrow cells, and mesothelium, we hypothesised that this might be important for homeostasis of adult tissues; hence, we deleted the gene ubiquitously in young and adult mice. Within just a few days, the mice suffered glomerulosclerosis, atrophy of the exocrine pancreas and spleen, severe reduction in bone and fat, and failure of erythropoiesis. FACS and culture experiments showed that Wt1 has an intrinsic role in both haematopoietic and mesenchymal stem cell lineages and suggest that defects within these contribute to the phenotypes we observe. We propose that glomerulosclerosis arises in part through down regulation of nephrin, a known Wt1 target gene. Protein profiling in mutant serum showed that there was no systemic inflammatory or nutritional response in the mutant mice. However, there was a dramatic reduction in circulating IGF-1 levels, which is likely to contribute to the bone and fat phenotypes. The reduction of IGF-1 did not result from a decrease in circulating GH, and there is no apparent pathology of the pituitary and adrenal glands. These findings 1) suggest that Wt1 is a major regulator of the homeostasis of some adult tissues, through both local and systemic actions; 2) highlight the differences between foetal and adult tissue regulation; 3) point to the importance of adult mesenchyme in tissue turnover., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2011
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49. A wt1-controlled chromatin switching mechanism underpins tissue-specific wnt4 activation and repression.
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Essafi A, Webb A, Berry RL, Slight J, Burn SF, Spraggon L, Velecela V, Martinez-Estrada OM, Wiltshire JH, Roberts SG, Brownstein D, Davies JA, Hastie ND, and Hohenstein P
- Abstract
Wt1 regulates the epithelial-mesenchymal transition (EMT) in the epicardium and the reverse process (MET) in kidney mesenchyme. The mechanisms underlying these reciprocal functions are unknown. Here, we show in both embryos and cultured cells that Wt1 regulates Wnt4 expression dichotomously. In kidney cells, Wt1 recruits Cbp and p300 as coactivators; in epicardial cells it enlists Basp1 as a corepressor. Surprisingly, in both tissues, Wt1 loss reciprocally switches the chromatin architecture of the entire Ctcf-bounded Wnt4 locus, but not the flanking regions; we term this mode of action "chromatin flip-flop." Ctcf and cohesin are dispensable for Wt1-mediated chromatin flip-flop but essential for maintaining the insulating boundaries. This work demonstrates that a developmental regulator coordinates chromatin boundaries with the transcriptional competence of the flanked region. These findings also have implications for hierarchical transcriptional regulation in development and disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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50. Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.
- Author
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Welsh M, Moffat L, McNeilly A, Brownstein D, Saunders PT, Sharpe RM, and Smith LB
- Subjects
- Animals, Male, Mice, Mice, Knockout, Mitosis physiology, Prostate metabolism, Prostate pathology, Prostatic Diseases metabolism, Prostatic Diseases pathology, Receptors, Androgen metabolism, Disease Models, Animal, Myocytes, Smooth Muscle metabolism, Prostatic Diseases genetics, Receptors, Androgen genetics
- Abstract
Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.
- Published
- 2011
- Full Text
- View/download PDF
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