Skeleton of an unusual cat-sized marsupial relative (Metatheria: Marsupialiformes) from the middle Eocene (Lutetian: 44-43 million years ago) of Turkey

We describe a near-complete, three-dimensionally preserved skeleton of a metatherian (relative of modern marsupials) from the middle Eocene (Lutetian: 44–43 million years ago) Lülük member of the Uzunçarşıdere Formation, central Turkey. With an estimated body mass of 3–4 kg, about the size of a domestic cat (Felis catus) or spotted quoll (Dasyurus maculatus), it is an order of magnitude larger than the largest fossil metatherians previously known from the Cenozoic of the northern hemisphere. This new taxon is characterised by large, broad third premolars that probably represent adaptations for hard object feeding (durophagy), and its craniodental morphology suggests the capacity to generate high bite forces. Qualitative and quantitative functional analyses of its postcranial skeleton indicate that it was probably scansorial and relatively agile, perhaps broadly similar in locomotor mode to the spotted quoll, but with a greater capacity for climbing and grasping. Bayesian phylogenetic analysis of a total evidence dataset comprising 259 morphological characters and 9kb of DNA sequence data from five nuclear protein-coding genes, using both undated and “tip-and-node dating” approaches, place the new taxon outside the marsupial crown-clade, but within the clade Marsupialiformes. It demonstrates that at least one metatherian lineage evolved to occupy the small-medium, meso- or hypo-carnivore niche in the northern hemisphere during the early Cenozoic, at a time when there were numerous eutherians (placentals and their fossil relatives) filling similar niches. However, the known mammal fauna from Uzunçarşıdere Formation appears highly endemic, and geological evidence suggests that this region of Turkey was an island for at least part of the early Cenozoic, and so the new taxon may have evolved in isolation from potential eutherian competitors. Nevertheless, the new taxon reveals previously unsuspected ecomorphological disparity among northern hemisphere metatherians during the first half of the Cenozoic

Small Theropod Teeth from the Late Cretaceous of the San Juan Basin, Northwestern New Mexico and Their Implications for Understanding Latest Cretaceous Dinosaur Evolution

Studying the evolution and biogeographic distribution of dinosaurs during the latest Cretaceous is critical for better understanding the end-Cretaceous extinction event that killed off all non-avian dinosaurs. Western North America contains among the best records of Late Cretaceous terrestrial vertebrates in the world, but is biased against small-bodied dinosaurs. Isolated teeth are the primary evidence for understanding the diversity and evolution of small-bodied theropod dinosaurs during the Late Cretaceous, but few such specimens have been well documented from outside of the northern Rockies, making it difficult to assess Late Cretaceous dinosaur diversity and biogeographic patterns. We describe small theropod teeth from the San Juan Basin of northwestern New Mexico. These specimens were collected from strata spanning Santonian - Maastrichtian. We grouped isolated theropod teeth into several morphotypes, which we assigned to higher-level theropod clades based on possession of phylogenetic synapomorphies. We then used principal components analysis and discriminant function analyses to gauge whether the San Juan Basin teeth overlap with, or are quantitatively distinct from, similar tooth morphotypes from other geographic areas. The San Juan Basin contains a diverse record of small theropods. Late Campanian assemblages differ from approximately coeval assemblages of the northern Rockies in being less diverse with only rare representatives of troodontids and a Dromaeosaurus-like taxon. We also provide evidence that erect and recurved morphs of a Richardoestesia-like taxon represent a single heterodont species. A late Maastrichtian assemblage is dominated by a distinct troodontid. The differences between northern and southern faunas based on isolated theropod teeth provide evidence for provinciality in the late Campanian and the late Maastrichtian of North America. However, there is no indication that major components of small-bodied theropod diversity were lost during the Maastrichtian in New Mexico. The same pattern seen in northern faunas, which may provide evidence for an abrupt dinosaur extinction

Blockade of PD1 and TIM3 Restores Innate and Adaptive Immunity in Patients With Acute Alcoholic Hepatitis

BACKGROUND &amp; AIMS: Susceptibility to bacterial infection is a feature of alcohol-related liver disease (ALD). Programmed cell death 1 (PDCD1, also known as PD1), the T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3, also known as hepatitis A virus cellular receptor 2, HAVCR2) and their respective ligands-CD274 (also known as PDL1) and galectin-9-are inhibitory receptors that regulate the balance between protective immunity and host immune-mediated damage. However, their sustained hyper-expression promotes immune exhaustion and paralysis. We investigated the role of these immune inhibitory receptors in driving immune impairments in patients with ALD.METHODS: In a prospective study, we collected blood samples from 20 patients with acute alcoholic hepatitis (AAH), 16 patients with stable advanced alcohol-related cirrhosis (ARC), and 12 healthy individuals (controls). Whole blood or peripheral blood mononuclear cells were assessed for expression of PD1, PDL1, TIM3, galectin-9, and toll-like receptors (TLRs) on subsets of innate and adaptive immune effector cells. We measured antibacterial immune responses to lipopolysaccharide (endotoxin) using ELISpot assays, and used flow cytometry to quantify cytokine production, phagocytosis and oxidative burst in the presence or absence of blocking antibodies against PD1 or TIM3.RESULTS: Antibacterial innate and adaptive immune responses were greatly reduced in patients with AAH, compared with controls, whereas patients with ARC had less-severe dysfunctions in innate immune effector cells and preserved functional T-cell responses. Fewer T cells from patients with AAH produced interferon-γ (IFNγ) in response to LPS, compared with controls. Furthermore, patients with AAH had greater numbers of IL10-producing T cells, and reduced levels of neutrophil phagocytosis and oxidative burst in response to Escherichia coli stimulation, compared to controls. T cells from patients with AAH, but not ARC, expressed higher levels of PD1 and PDL1, or TIM3 and galectin-9, than T cells from controls. Antibodies against PD1 and TIM3 restored T-cell production of IFNγ, reduced the numbers of IL10-producing T cells, and increased neutrophil antimicrobial activities. Circulating levels of endotoxin in plasma from patients with AAH caused over expression of immune inhibitory receptors on T cells via TLR4 binding to CD14+ monocytes.CONCLUSIONS: Antibacterial immune responses are impaired in patients with AAH. Lymphocytes from these patients express high levels of immune inhibitory receptors, produce lower levels of IFNγ, and have increased IL10 production due to chronic endotoxin exposure. These effects can be reversed by blocking PD1 and TIM3, which increase the antimicrobial activities of T cells and neutrophils.</p

The origin of Afro-Arabian 'Didelphimorph' marsupials

New specimens of Peratherium africanum from Early Oligocene deposits of the Fayum, Egypt, provide key information on the relationships of the species. These include the first maxilla to be found and two additional dentaries. The maxilla can be demonstrated to belong to the same species as the holotype dentary by study of the occlusal relationships of upper and lower molars. It can be shown by several synapomorphies that P. africanum is the sister species to European Bartonian–Rupelian Peratherium lavergnense. P. africanum therefore belongs to the 'didelphimorph' family Herpetotheriidae, not to the peradectimorph family Peradectidae. The genus Qatranitherium, previously erected for this species alone, is here synonymized with Peratherium. Comparison with 'didelphimorphian' taxa from early Paleogene deposits of South America suggests more remote relationships, indicating an origin for P. africanum by dispersal from Europe as originally envisaged. The more precise relationships deduced here help to constrain the time interval for dispersal to Afro-Arabia, probably during the earliest Oligocene sea-level lo