23 research outputs found
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
The biostratigraphic and palaeoenvironmental significance of the late middle jurassic-early late cretaceous palynology of the Great Australian Bight Region
The late Middle Jurassic to early Late Cretaceous non-marine
and marine sediments in the Great Australian Bight region
were deposited during initial rifting between Australia and
Antarctica. These sediments have been drilled and logged in
Echidna-1 and Platypus-1 in the Duntroon Embayment. Potoroo-1
on the northernmost margin of the Great Australian Bight
Basin, and Jerboa-1 in the Eyre Sub-basin.
In these logged wells is recorded a conformable sequence
through the Murospora florida, Retitriletes watherooensis,
Cicatricosisporites australiensis, Foraminisporis
wonthaggiensis and Cyclosporites hughesii spore-pollen Zones.
The Coptospora paradoxa spore-pollen Zone is present in
Platypus-1 and Potoroo-1, and three wells(Jerboa-1,
Platypus-1, Potoroo-1) include the Phimopollenites pannosus
and Appendicisporites distocarinatus spore-pollen Zones. In
these three zones, dinoflagellates represent the
Canninginopsis denticulata, Pseudoceratium ludbrookiae and
Diconodinium multispinum Zones.
The palynological zonation of the wells in this study assumes
that the first appearance of certain spore-pollen species in
the Great Australian Bight region were reliable, in the sense
that they corresponded with those elsewhere in the continent
as summarised in Helby et al. (1987). The ages of these first
appearance datums have been critically re-evaluated to allow
correlation of the wells with the standard geological time
scale.
The age control established by using palynological
information suggests that depositional history of the Great
Australian Bight region commenced in the Callovian, and this
sequence of non-marine sedimentation continued without
interference through until the early Aptian. Albian marine
sedimentation (recorded in Jerboa-1 and Potoroo-1) most
probably relates to a major marine transgression in the Eucla
Basin. In Platypus-1 age equivalent sediments are non-marine.
Cenomanian marine sediments indicate a marine transgression
that probably encroached from the west of the continent
following the separation of Australia and Antarctica.
The establishment of reliable spore-pollen first appearance
datums showed that the ranges of other species are at
variance with those elsewhere on the continent. For some
species, a west-east variation in the ranges suggested a
migration path across the Great Australian Bight region in
the Callovian to early Aptian, which corresponded to a
movement of flora from high to low latitudes. This migration
path from the west to the east appears to have been
maintained until the Cenomanian, even though it no longer
involved a latitudinal gradient. This seems to imply that the
unique, unstable rift environment was the chief vehicle of
floral channeling, perhaps reinforced by the encroaching
marine environment from the west into the region during the
younger interval.
During the Callovian to Berriasian vegetation in the Great
Australian Bight region was dominated by the gymnosperm
family Araucariaceae. A possible increase in precipitation
during the late Berriasian saw a decrease in the
Araucariaceae, with podocarps taking over the dominant role.
Albian and Cenomanian vegetation in the Great Australian
Bight region was also dominated by podocarpaceous
gymnosperms, with the fern family Gleicheniaceae being the
major component of the local vegetation. The dinoflagellate
assemblages at this time are typified by taxa of the
Heterosphaeridium Superzone of Helby et al. (1987)
Early Cretaceous polar biotas of Victoria, southeastern Australiaâan overview of research to date
Although Cretaceous fossils (coal excluded) from Victoria, Australia, were first reported in the 1850s, it was not until the 1950s that detailed studies
of these fossils were undertaken. Numerous fossil localities have been identified in Victoria since the 1960s, including the Koonwarra Fossil
Bed (Strzelecki Group) near Leongatha, the Dinosaur Cove and Eric the Red West sites (Otway Group) at Cape Otway, and the Flat Rocks site
(Strzelecki Group) near Cape Paterson. Systematic exploration over the past five decades has resulted in the collection of thousands of fossils representing
various plants, invertebrates and vertebrates. Some of the best-preserved and most diverse HauterivianâBarremian floral assemblages in
Australia derive from outcrops of the lower Strzelecki Group in the Gippsland Basin. The slightly younger Koonwarra Fossil Bed (Aptian) is a
Konservat-LagerstÀtte that also preserves abundant plants, including one of the oldest known flowers. In addition, insects, crustaceans (including
the only syncaridans known from Australia between the Triassic and the present), arachnids (including Australiaâs only known opilione), the stratigraphically
youngest xiphosurans from Australia, bryozoans, unionoid molluscs and a rich assemblage of actinopterygian fish are known from the
Koonwarra Fossil Bed. The oldest knownâand only Mesozoicâfossil feathers from the Australian continent constitute the only evidence for tetrapods
at Koonwarra. By contrast, the BarremianâAptian-aged deposits at the Flat Rocks site, and the AptianâAlbian-aged strata at the Dinosaur
Cove and Eric the Red West sites, are all dominated by tetrapod fossils, with actinopterygians and dipnoans relatively rare. Small ornithopod
(=basal neornithischian) dinosaurs are numerically common, known from four partial skeletons and a multitude of isolated bones. Aquatic meiolaniform
turtles constitute another prominent faunal element, represented by numerous isolated bones and articulated carapaces and plastrons. More
than 50 specimensâmostly lower jawsâevince a high diversity of mammals, including monotremes, a multituberculate and several enigmatic
ausktribosphenids. Relatively minor components of these fossil assemblages are diverse theropods (including birds), rare ankylosaurs and ceratopsians,
pterosaurs, non-marine plesiosaurs and a lepidosaur. In the older strata of the upper Strzelecki Group, temnospondyl amphibiansâthe youngest
known worldwideâare a conspicuous component of the fauna, whereas crocodylomorphs appear to be present only in up-sequence deposits of
the Otway Group. Invertebrates are uncommon, although decapod crustaceans and unionoid bivalves have been described. Collectively, the Early
Cretaceous biota of Victoria provides insights into a unique Mesozoic high-latitude palaeoenvironment and elucidates both palaeoclimatic and
palaeobiogeographic changes throughout more than 25 million years of geological time.We are grateful to the
National Geographic Society and private donors for
funding
Early Cretaceous polar biotas of Victoria, southeastern Australiaâan overview of research to date
<p>Poropat, S.F., Martin, S.K., Tosolini, A.-M.P., Wagstaff, B.E, Bean, L.B., Kear, B.P., Vickers-Rich, P. & Rich, T.H., May 2018. Early Cretaceous polar biotas of Victoria, southeastern Australiaâan overview of research to date. <i>Alcheringa 42</i>, 158â230. ISSN 0311-5518.</p> <p>Although Cretaceous fossils (coal excluded) from Victoria, Australia, were first reported in the 1850s, it was not until the 1950s that detailed studies of these fossils were undertaken. Numerous fossil localities have been identified in Victoria since the 1960s, including the Koonwarra Fossil Bed (Strzelecki Group) near Leongatha, the Dinosaur Cove and Eric the Red West sites (Otway Group) at Cape Otway, and the Flat Rocks site (Strzelecki Group) near Cape Paterson. Systematic exploration over the past five decades has resulted in the collection of thousands of fossils representing various plants, invertebrates and vertebrates. Some of the best-preserved and most diverse HauterivianâBarremian floral assemblages in Australia derive from outcrops of the lower Strzelecki Group in the Gippsland Basin. The slightly younger Koonwarra Fossil Bed (Aptian) is a <i>Konservat-LagerstĂ€tte</i> that also preserves abundant plants, including one of the oldest known flowers. In addition, insects, crustaceans (including the only syncaridans known from Australia between the Triassic and the present), arachnids (including Australiaâs only known opilione), the stratigraphically youngest xiphosurans from Australia, bryozoans, unionoid molluscs and a rich assemblage of actinopterygian fish are known from the Koonwarra Fossil Bed. The oldest knownâand only Mesozoicâfossil feathers from the Australian continent constitute the only evidence for tetrapods at Koonwarra. By contrast, the BarremianâAptian-aged deposits at the Flat Rocks site, and the AptianâAlbian-aged strata at the Dinosaur Cove and Eric the Red West sites, are all dominated by tetrapod fossils, with actinopterygians and dipnoans relatively rare. Small ornithopod (=basal neornithischian) dinosaurs are numerically common, known from four partial skeletons and a multitude of isolated bones. Aquatic meiolaniform turtles constitute another prominent faunal element, represented by numerous isolated bones and articulated carapaces and plastrons. More than 50 specimensâmostly lower jawsâevince a high diversity of mammals, including monotremes, a multituberculate and several enigmatic ausktribosphenids. Relatively minor components of these fossil assemblages are diverse theropods (including birds), rare ankylosaurs and ceratopsians, pterosaurs, non-marine plesiosaurs and a lepidosaur. In the older strata of the upper Strzelecki Group, temnospondyl amphibiansâthe youngest known worldwideâare a conspicuous component of the fauna, whereas crocodylomorphs appear to be present only in up-sequence deposits of the Otway Group. Invertebrates are uncommon, although decapod crustaceans and unionoid bivalves have been described. Collectively, the Early Cretaceous biota of Victoria provides insights into a unique Mesozoic high-latitude palaeoenvironment and elucidates both palaeoclimatic and palaeobiogeographic changes throughout more than 25 million years of geological time.</p> <p><i>Stephen F. Poropat*â [</i><i>[email protected]</i><i>;</i><i>[email protected]</i><i>], Faculty of Science, Engineering and Technology, Swinburne University of Technology, John St, Hawthorn, Victoria 3122, Australia; Sarah K. Martin*⥠[</i><i>[email protected]</i><i>;</i><i>[email protected]</i><i>] Geological Survey of Western Australia, 100 Plain St, East Perth, Western Australia 6004, Australia; Anne-Marie P. Tosolini [</i><i>[email protected]</i><i>] and Barbara E. Wagstaff [</i><i>[email protected]</i><i>] School of Earth Sciences, The University of Melbourne, Melbourne, Victoria 3010, Australia; Lynne B. Bean [</i><i>[email protected]</i><i>] Research School of Earth Sciences, Australian National University, Acton, Canberra, Australian Capital Territory 2001, Australia; Benjamin P. Kear [</i><i>[email protected]</i><i>] Museum of Evolution, Uppsala University, NorbyvĂ€gen 16, Uppsala SE-752 36, Sweden; Patricia Vickers-Rich§ [</i><i>[email protected]</i><i>;</i><i>[email protected]</i><i>] Faculty of Science, Engineering and Technology, Swinburne University of Technology, John St, Hawthorn, Victoria 3122, Australia; Thomas H. Rich [</i><i>[email protected]</i><i>] Museum Victoria, PO Box 666, Melbourne, Victoria 3001, Australia. *These authors contributed equally to this work. â Also affiliated with: Australian Age of Dinosaurs Museum of Natural History, Lot 1 Dinosaur Drive, PO Box 408, Winton, Queensland 4735, Australia. âĄAlso affiliated with: Earth and Planetary Sciences, Western Australian Museum, Welshpool, Western Australia 6101, Australia. §Also affiliated with: School of Earth, Atmosphere and Environment, Monash University, Melbourne, Victoria 3800, Australia.</i></p
Prevalence and predictive factors for renouncing medical care in poor populations of Cayenne, French Guiana
The mandible and dentition of the Early Cretaceous monotreme Teinolophos trusleri
The monotreme Teinolophos trusleri Rich, Vickers-Rich, Constantine, Flannery, Kool & van Klaveren, 1999 from the Early Cretaceous of Australia
is redescribed and reinterpreted here in light of additional specimens of that species and compared with the exquisitely preserved Early Cretaceous
mammals from Liaoning Province, China. Together, this material indicates that although T. trusleri lacked a rod of postdentary bones contacting
the dentary, as occurs in non-mammalian cynodonts and basal mammaliaforms, it did not share the condition present in all living mammals, including
monotremes, of having the three auditory ossicles, which directly connect the tympanic membrane to the fenestra ovalis, being freely suspended
within the middle ear cavity. Rather, T. trusleri appears to have had an intermediate condition, present in some Early Cretaceous mammals from
Liaoning, in which the postdentary bones cum ear ossicles retained a connection to a persisting Meckelâs cartilage although not to the dentary.
Teinolophos thus indicates that the condition of freely suspended auditory ossicles was acquired independently in monotremes and therian mammals.
Much of the anterior region of the lower jaw of Teinolophos is now known, along with an isolated upper ultimate premolar. The previously
unknown anterior region of the jaw is elongated and delicate as in extant monotremes, but differs in having at least seven antemolar teeth, which
are separated by distinct diastemata. The dental formula of the lower jaw of Teinolophos trusleri as now known is i2 c1 p4 m5. Both the deep
lower jaw and the long-rooted upper premolar indicate that Teinolophos, unlike undoubted ornithorhynchids (including the extinct Obdurodon),
lacked a bill.The Committee for Research and
Exploration of the National Geographic Society and the
Australian Research Council provided much of the
funding needed for the fieldwork carried out at the Flat
Rocks locality. We acknowledge travel funding provided
by the International Synchrotron Access Program managed
by the Australian Synchrotron and funded by the
Australian Government
Palaeoenvironments and palaeocommunities from Lower Cretaceous high-latitude sites, Otway Basin, southeastern Australia
Cheirolepidiacean foliage and pollen from Cretaceous high-latitudes of southeastern Australia
Cheirolepidiaceae leaves and pollen are recorded from ValanginianâAlbian strata of southeastern Australia that were deposited at high-latitudes under cool, moist climates in contrast to the semi-arid or coastal habitats preferred by many northern Gondwanan and Laurasian representatives of this group. Leaves of this family are characterized by thick cuticles and cyclocytic stomata with randomly oriented apertures, arranged in scattered or longitudinal rows or bands. Stomata are deeply sunken and surrounded by four to six subsidiary cells that bear one or two ranks of prominent overarching papillae, which may constrict the mouth of the pit. Three new taxa (Otwayia denticulata Tosolini, Cheirolepidiaceae cuticle sp. A and sp. B) are distinguished based on cuticular features, adding to several previously documented cheirolepid conifers in the Early Cretaceous of eastern Australia. Cheirolepidiaceae foliage is preserved predominantly in fluvial floodbasin settings and is interpreted to be derived from small trees occupying disturbed or low-nutrient sites. The foliage is associated with Classopollis/Corollina pollen and roots characterized by prominent mycorrhizal nodules. A Cenomanian Classopollis type recognised from Bathurst Island, Northern Australia, is recorded for the first time from the Early Cretaceous Eumeralla Formation, Otway Basin. Classopollis locally is rare in ValanginianâBarremian strata of Boola Boola, Gippsland, but constitutes up to 14% of the palynomorph assemblage in Albian strata. This indicates that the family was locally abundant in cool southern high-latitude climates of the Mesozoic, contrary to previous reports of its rarity in this region.Reconstructing the lost forests of Antarctica: the palaeoecology, anatomy and phylogeny of the iconic Glossopteris floraExceptional permineralized biotas - windows into the evolution and functional diversity of terrestrial ecosystems through tim