The marsupial family Diprotodontidae (Diprotodontia, Vombatiformes) is a group of extinct large-bodied (60-2500 kg) wombat-like herbivores that were common and geographically widespread in Cenozoic ...fossil deposits of Australia and New Guinea. Typically they are regarded to be gregarious, terrestrial quadrupeds and have been likened in body form among placental groups to sheep, rhinoceros and hippopotami. Arguably, one of the best represented species is the zygomaturine diprotodontid Nimbadon lavarackorum which is known from exceptionally well-preserved cranial and postcranial material from the middle Miocene cave deposit AL90, in the Riversleigh World Heritage Area, northwestern Queensland. Here we describe and functionally analyse the appendicular skeleton of Nimbadon lavarackorum and reveal a far more unique lifestyle for this plesiomorphic and smallest of diprotodontids. Striking similarities are evident between the skeleton of Nimbadon and that of the extant arboreal koala Phascolarctos cinereus, including the powerfully built forelimbs, highly mobile shoulder and elbow joints, proportionately large manus and pes (both with a semi-opposable digit I) and exceedingly large, recurved and laterally compressed claws. Combined with the unique (among australidelphians) proportionately shortened hindlimbs of Nimbadon, these features suggest adept climbing ability, probable suspensory behaviour, and an arboreal lifestyle. At approximately 70 kg, Nimbadon is the largest herbivorous mammal to have occupied the forest canopies of Australia - an ecological niche that is no longer occupied in any Australian ecosystem and one that further expands the already significant niche diversity displayed by marsupials during the Cenozoic.
We describe new cranial and post-cranial marsupial fossils from the early Eocene Tingamarra Local Fauna in Australia and refer them to Djarthia murgonensis, which was previously known only from ...fragmentary dental remains.
The new material indicates that Djarthia is a member of Australidelphia, a pan-Gondwanan clade comprising all extant Australian marsupials together with the South American microbiotheres. Djarthia is therefore the oldest known crown-group marsupial anywhere in the world that is represented by dental, cranial and post-cranial remains, and the oldest known Australian marsupial by 30 million years. It is also the most plesiomorphic known australidelphian, and phylogenetic analyses place it outside all other Australian marsupials.
As the most plesiomorphic and oldest unequivocal australidelphian, Djarthia may approximate the ancestral morphotype of the Australian marsupial radiation and suggests that the South American microbiotheres may be the result of back-dispersal from eastern Gondwana, which is the reverse of prevailing hypotheses.
Exceptionally well-preserved skulls and postcranial elements of a new species of the plesiomorphic stem macropodiform Balbaroo have been recovered from middle Miocene freshwater limestone deposits in ...the Riversleigh World Heritage Area of northwestern Queensland, Australia. This constitutes the richest intraspecific sample for any currently known basal "kangaroo", and, along with additional material referred to Balbaroo fangaroo, provides new insights into structural variability within the most prolific archaic macropodiform clade--Balbaridae. Qualitative and metric evaluations of taxonomic boundaries demonstrate that the previously distinct species Nambaroo bullockensis is a junior synonym of B. camfieldensis. Furthermore, coupled Maximum Parsimony and Bayesian phylogenetic analyses reveal that our new Balbaroo remains represent the most derived member of the Balbaroo lineage, and are closely related to the middle Miocene B. camfieldensis, which like most named balbarid species is identifiable only from isolated jaws. The postcranial elements of Balbaroo concur with earlier finds of the stratigraphically oldest balbarid skeleton, Nambaroo gillespieae, and suggest that quadrupedal progression was a primary gait mode as opposed to bipedal saltation. All Balbaroo spp. have low-crowned bilophodont molars, which are typical for browsing herbivores inhabiting the densely forested environments envisaged for middle Miocene northeastern Australia.
Previously we showed that natural compound α-penta-galloyl-glucose (α-PGG) and its synthetic derivative 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-α-D-glucopyranose (6Cl-TGQ) act to improve insulin ...signaling in adipocytes by increasing glucose transport. In this study, we investigated the mechanism of actions of α-PGG and 6Cl-TGQ on insulin secretion.
Mouse islets and/or INS-1832/13 beta-cells were used to test the effects of our compounds on glucose-stimulated insulin secretion (GSIS), intracellular calcium Ca
using fura-2AM, glucose transport activity via a radioactive glucose uptake assay, intracellular ATP/ADP, and extracellular acidification (ECAR) and mitochondrial oxygen consumption rates (OCAR) using Seahorse metabolic analysis.
Both compounds reduced GSIS in beta-cells without negatively affecting cell viability. The compounds primarily diminished glucose uptake into islets and beta-cells. Despite insulin-like effects in the peripheral tissues, these compounds do not act through the insulin receptor in islets. Further interrogation of the stimulus-secretion pathway showed that all the key metabolic factors involved in GSIS including ECAR, OCAR, ATP/ADP ratios, and Ca
of INS-1832/13 cells were diminished after the compound treatment.
The compounds suppress glucose uptake of the beta-cells, which consequently slows down the rates of glycolysis and ATP synthesis, leading to decrease in Ca
and GSIS. The difference between adipocytes and beta-cells in effects on glucose uptake is of great interest. Further structural and functional modifications could produce new compounds with optimized therapeutic potentials for different target cells. The higher potency of synthetic 6Cl-TGQ in enhancing insulin signaling in adipocytes but lower potency in reducing glucose uptake in beta-cells compared to α-PGG suggests the feasibility of such an approach.
Instances of dwarfism in the fossil record are of interest to palaeontologists because they often provide insight into aspects of palaeoecology. Fossil species of Australian-Pacific mekosuchine genus ...Mekosuchus have been described as dwarf, primarily terrestrial crocodiles, in contrast with the nearly ubiquitous semi-aquatic habitus of extant crocodilians (Willis 1997). This hypothesis has been difficult to test because of limited knowledge of the cranial and postcranial skeleton of extinct taxa and the continuous nature of crocodilian growth. New crocodilian vertebral material from Riversleigh, northwestern Queensland, tentatively referred to Mekosuchus whitehunterensis, displays morphological maturity indicative of adult snout-vent length little over a half-meter, proportionally smaller than extant dwarf taxa. Further, this material displays morphology that indicates a relatively large epaxial neck musculature for its body-size. These attributes suggest this dwarf mekosuchine employed unusual feeding behaviours. The ability to perform normal death-roll, de-fleshing behaviours would be limited in a mekosuchine of such small size. Given the powerful neck muscles and other anatomical features, it is more likely that this mekosuchine killed and/or dismembered its prey using a relatively forceful lifting and shaking of the head.
Morphological shifts observed in the fossil record of a lineage potentially indicate concomitant shifts in ecology of that lineage. Mekosuchine crocodiles of Cenozoic Australia display departures ...from the typical eusuchian body-plan both in the cranium and postcranium. Previous qualitative studies have suggested that these crocodiles had a more terrestrial habitus than extant crocodylians, yet the capacity of mekosuchine locomotion remains to be tested. Limb bone shape, such as diaphyseal cross-section and curvature, has been related to habitual use and locomotory function across a wide variety of taxa. Available specimens of mekosuchine limbs, primarily humeri, are distinctly columnar compared with those of extant crocodylians. Here we apply a quantitative approach to biomechanics in mekosuchine taxa using both geomorphic morphometric and finite element methods to measure bone shape and estimate locomotory stresses in a comparative context. Our results show mekosuchines appear to diverge from extant semi-aquatic saltwater and freshwater crocodiles in cross-sectional geometry of the diaphysis and generate different structural stresses between models that simulate sprawling and high-walk gaits. The extant crocodylians display generally rounded cross-sectional diaphyseal outlines, which may provide preliminary indication of resistance to torsional loads that predominate during sprawling gait, whereas mekosuchine humeri appear to vary between a series of elliptical outlines. Mekosuchine structural stresses are comparatively lower than those of the extant crocodylians and reduce under high-walk gait in some instances. This appears to be a function of bending moments induced by differing configurations of diaphyseal curvature. Additionally, the neutral axis of structural stresses is differently oriented in mekosuchines. This suggests a shift in the focus of biomechanical optimisation, from torsional to axial loadings. Our results lend quantitative support to the terrestrial habitus hypothesis in so far as they suggest that mekosuchine humeri occupied a different morphospace than that associated with the semi-aquatic habit. The exact adaptational trajectory of mekosuchines, however, remains to be fully quantified. Novel forms appear to emerge among mekosuchines during the late Cenozoic. Their adaptational function is considered here; possible applications include navigation of uneven terrain and burrowing.
There are concerns regarding increased cancer incidence in patients treated with ezetimibe, an inhibitor of the absorption of dietary cholesterol. Here we tested the hypothesis that ezetimibe will ...accelerate mammary tumorigenesis in rats. The drug was administered at a dose of 1 ppm in an AIN‐93G diet that contained 0.3% cholesterol. This experimental diet and control diets that contained either no additions or cholesterol or ezetimibe only, were fed to groups of 30 Sprague‐Dawley rats 3 days after they were treated with 50 mg/kg methylnitrosourea (MNU). All rats were euthanized 22 weeks after MNU administration. Tumor multiplicity was significantly smaller in rats fed cholesterol than those fed no cholesterol (1.84 ± 0.42 vs. 3.86 ± 0.86 respectively, P < 0.05), but was significantly greater in the cholesterol/ezetimibe group than the group fed only cholesterol (3.48 ± 0.59 vs. 1.84 ± 0.42 respectively, P < 0.04). The average weight of tumors/rat was also significantly larger in the cholesterol/ezetimibe group than those fed cholesterol alone (5.67 ± 1.15 vs. 2.56 ± 0.71 respectively, P < 0.04). As expected, ezetimibe prevented the cholesterol raising effect of the dietary cholesterol. These results show that ezetimibe reverses the inhibitory effect of dietary cholesterol on the development of rat mammary tumors.
Thylacinidae is an extinct family of Australian and New Guinean marsupial carnivores, comprizing 12 known species, the oldest of which are late Oligocene (∼24 Ma) in age. Except for the recently ...extinct thylacine (Thylacinus cynocephalus), most are known from fragmentary craniodental material only, limiting the scope of biomechanical and ecological studies. However, a particularly well-preserved skull of the fossil species Nimbacinus dicksoni, has been recovered from middle Miocene (∼16-11.6 Ma) deposits in the Riversleigh World Heritage Area, northwestern Queensland. Here, we ask whether N. dicksoni was more similar to its recently extinct relative or to several large living marsupials in a key aspect of feeding ecology, i.e., was N. dicksoni a relatively small or large prey specialist. To address this question we have digitally reconstructed its skull and applied three-dimensional Finite Element Analysis to compare its mechanical performance with that of three extant marsupial carnivores and T. cynocephalus. Under loadings adjusted for differences in size that simulated forces generated by both jaw closing musculature and struggling prey, we found that stress distributions and magnitudes in the skull of N. dicksoni were more similar to those of the living spotted-tailed quoll (Dasyurus maculatus) than to its recently extinct relative. Considering the Finite Element Analysis results and dental morphology, we predict that N. dicksoni likely occupied a broadly similar ecological niche to that of D. maculatus, and was likely capable of hunting vertebrate prey that may have exceeded its own body mass.
Australian Oligo-Miocene mekosuchines (Crocodylia; Crocodyloidea) display wide diversity in cranial shape and inferred hunting strategies. Terrestrial habitus has been inferred for these distinctive ...predators. A direct morphological signal for locomotion can be expected in the postcrania, particularly the pelvic and pectoral girdles. Here we describe fossil materials of the girdles, which chart their morphological variation in the subfamily from Eocene through to Middle Miocene. Over this period, both girdles undergo significant morphological changes. Notably, an enclosed, ventrally orientated acetabulum in the ilium is developed in one lineage. This recapitulates the erect parasagittal configuration of the pelvic limb seen in many Mesozoic crocodylomorph lineages, suggesting consistent use of erect high-walking in these mekosuchines. Other pelves from the same Oligo-Miocene deposits display morphology closer to modern crocodilians, suggesting a partitioning of locomotory strategy among sympatric mekosuchines. Plesiomorphic and derived pelvic girdles are distinguishable by parsimony analysis, and the earliest examples of the mekosuchine pelvis more closely resemble gavialids and alligatorids while latter forms converge on crown group crocodylids in the morphology of the iliac crest. This suggests that a revaluation of the base relationship of Mekosuchinae within Eusuchia is necessary.
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