Scleromochlus and the early evolution of Pterosauromorpha.

Pterosaurs, the first vertebrates to evolve powered flight, were key components of Mesozoic terrestrial ecosystems from their sudden appearance in the Late Triassic until their demise at the end of the Cretaceous1-6. However, the origin and early evolution of pterosaurs are poorly understood owing to a substantial stratigraphic and morphological gap between these reptiles and their closest relatives6, Lagerpetidae7. Scleromochlus taylori, a tiny reptile from the early Late Triassic of Scotland discovered over a century ago, was hypothesized to be a key taxon closely related to pterosaurs8, but its poor preservation has limited previous studies and resulted in controversy over its phylogenetic position, with some even doubting its identification as an archosaur9. Here we use microcomputed tomographic scans to provide the first accurate whole-skeletal reconstruction and a revised diagnosis of Scleromochlus, revealing new anatomical details that conclusively identify it as a close pterosaur relative1 within Pterosauromorpha (the lagerpetid + pterosaur clade). Scleromochlus is anatomically more similar to lagerpetids than to pterosaurs and retains numerous features that were probably present in very early diverging members of Avemetatarsalia (bird-line archosaurs). These results support the hypothesis that the first flying reptiles evolved from tiny, probably facultatively bipedal, cursorial ancestors1.

Inner ear biomechanics reveals a Late Triassic origin for mammalian endothermy.

Endothermy underpins the ecological dominance of mammals and birds in diverse environmental settings1,2. However, it is unclear when this crucial feature emerged during mammalian evolutionary history, as most of the fossil evidence is ambiguous3-17. Here we show that this key evolutionary transition can be investigated using the morphology of the endolymph-filled semicircular ducts of the inner ear, which monitor head rotations and are essential for motor coordination, navigation and spatial awareness18-22. Increased body temperatures during the ectotherm-endotherm transition of mammal ancestors would decrease endolymph viscosity, negatively affecting semicircular duct biomechanics23,24, while simultaneously increasing behavioural activity25,26 probably required improved performance27. Morphological changes to the membranous ducts and enclosing bony canals would have been necessary to maintain optimal functionality during this transition. To track these morphofunctional changes in 56 extinct synapsid species, we developed the thermo-motility index, a proxy based on bony canal morphology. The results suggest that endothermy evolved abruptly during the Late Triassic period in Mammaliamorpha, correlated with a sharp increase in body temperature (5-9 °C) and an expansion of aerobic and anaerobic capacities. Contrary to previous suggestions3-14, all stem mammaliamorphs were most probably ectotherms. Endothermy, as a crucial physiological characteristic, joins other distinctive mammalian features that arose during this period of climatic instability28.

Mosaic evolution underlies feliform morphological disparity.

Constraint is a fundamental concept in evolutionary theory. Morphology and ecology both are limited by functional, historical and developmental factors to a subset of the theoretical range species could occupy. Cat-like carnivorans (Feliformia) offer a unique opportunity to investigate phenotypic constraint, as several feliform clades are purported to be limited to generalized ecomorphological roles, while others possess extremely specialized durophagous (bone-crushing) and sabretooth morphology. We investigated the evolutionary history of feliforms by considering their phylogeny, morphological disparity and rates of evolution. We recover results that show a mosaic pattern exists in the degree of morphological disparity per anatomical region per clade and ecology. Non-hypercarnivores, such as viverrids (civets and genets), Malagasy euplerids and lophocyonids (extinct hypocarnivores), have the greatest dental disparity, while hypercarnivores (felids, nimravids, many hyaenids) have the lowest dental disparity but highest cranial and mandibular disparity (excluding dentition). However, high disparity is not necessarily associated with high rates of evolution, but instead with ecological radiations. We reveal that relationships between specialization and disparity are not as simple as past research has concluded. Instead, morphological disparity results from an anatomical mosaic of evolution, where different ecologies correlate with and likely channel unique patterns/combinations of disparity per anatomical partition.

Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma.

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.

A new hypothesis of dinosaur relationships and early dinosaur evolution.

For 130 years, dinosaurs have been divided into two distinct clades-Ornithischia and Saurischia. Here we present a hypothesis for the phylogenetic relationships of the major dinosaurian groups that challenges the current consensus concerning early dinosaur evolution and highlights problematic aspects of current cladistic definitions. Our study has found a sister-group relationship between Ornithischia and Theropoda (united in the new clade Ornithoscelida), with Sauropodomorpha and Herrerasauridae (as the redefined Saurischia) forming its monophyletic outgroup. This new tree topology requires redefinition and rediagnosis of Dinosauria and the subsidiary dinosaurian clades. In addition, it forces re-evaluations of early dinosaur cladogenesis and character evolution, suggests that hypercarnivory was acquired independently in herrerasaurids and theropods, and offers an explanation for many of the anatomical features previously regarded as notable convergences between theropods and early ornithischians.

The earliest bird-line archosaurs and the assembly of the dinosaur body plan.

The relationship between dinosaurs and other reptiles is well established, but the sequence of acquisition of dinosaurian features has been obscured by the scarcity of fossils with transitional morphologies. The closest extinct relatives of dinosaurs either have highly derived morphologies or are known from poorly preserved or incomplete material. Here we describe one of the stratigraphically lowest and phylogenetically earliest members of the avian stem lineage (Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle Triassic epoch. The anatomy of T. rhadinus provides key information that unites several enigmatic taxa from across Pangaea into a previously unrecognized clade, Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We demonstrate that several anatomical features long thought to characterize Dinosauria and dinosauriforms evolved much earlier, soon after the bird-crocodylian split, and that the earliest avemetatarsalians retained the crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and early pseudosuchians. Early avemetatarsalians were substantially more species-rich, widely geographically distributed and morphologically diverse than previously recognized. Moreover, several early dinosauromorphs that were previously used as models to understand dinosaur origins may represent specialized forms rather than the ancestral avemetatarsalian morphology.

SATurn: a modular bioinformatics framework for the design of robust maintainable web-based and standalone applications.

Summary: SATurn is a modular, open-source, bioinformatics platform designed to specifically address the problems of maintenance and longevity commonly associated with the development of simple tools funded by academic research grants. Applications developed in SATurn can be deployed as web-based tools, standalone applications or hybrid tools which have the benefits of both. Within the Structural Genomics Consortium we have utilized SATurn to create a bioinformatics portal which routinely supports a diverse group of scientists including those interested in structural biology, cloning, glycobiology and chemical biology. Availability and implementation: https://github.com/ddamerell53/SATurn. Supplementary information: Supplementary data are available at Bioinformatics online.

Intraocular pressure reference intervals in eyes of clinically normal miniature donkeys (Equus africanus asinus).

PURPOSE: To determine intraocular pressure (IOP) reference intervals in eyes of healthy miniature donkeys (Equus africanus asinus) via rebound and applanation tonometry. METHODS: Complete ophthalmic and physical examinations were performed by board-certified veterinary ophthalmologists. Inclusion criteria for animals participating in this study were dictated by the American Society for Veterinary Clinical Pathology (ASVCP) reference interval guidelines. Intraocular pressure estimates (TonoVet® and TonoPen XL® ) were obtained in both eyes. Forty animals (San Angelo group) received intramuscular xylazine hydrochloride 10% and auriculopalpebral (AP) nerve blocks prior to obtaining measurements. Twenty-two animals (Austin group) received no sedation or AP block. Statistical analysis followed ASVCP reference interval guidelines. Analysis was performed using the software sas V9 (SAS Institute Inc., Cary, NC, USA). RESULTS: Fifty-seven (114 eyes) healthy miniature donkeys were included in this study. The mean IOP ± standard deviation (SD) was 25.75 ± 5.70 mm Hg for rebound tonometry with reference limits of 14.34 and 37.15. The mean IOP ± SD was 20.69 ± 5.06 mm Hg for applanation tonometry with reference limits of 12.82 and 33.38. No significant difference in IOP was found between the Austin and San Angelo groups (P = .34). A significant difference was noted between rebound and applanation IOP estimates (P < .0001) with rebound tonometric values being higher. CONCLUSIONS: Reference intervals for IOP's were established for this species. Intraocular pressure readings obtained by the rebound tonometer were significantly higher than with applanation. Sedation and AP block did not affect IOP estimates.

Open data and digital morphology.

Over the past two decades, the development of methods for visualizing and analysing specimens digitally, in three and even four dimensions, has transformed the study of living and fossil organisms. However, the initial promise that the widespread application of such methods would facilitate access to the underlying digital data has not been fully achieved. The underlying datasets for many published studies are not readily or freely available, introducing a barrier to verification and reproducibility, and the reuse of data. There is no current agreement or policy on the amount and type of data that should be made available alongside studies that use, and in some cases are wholly reliant on, digital morphology. Here, we propose a set of recommendations for minimum standards and additional best practice for three-dimensional digital data publication, and review the issues around data storage, management and accessibility.

Herbivorous dinosaur jaw disparity and its relationship to extrinsic evolutionary drivers.

Morphological responses of nonmammalian herbivores to external ecological drivers have not been quantified over extended timescales. Herbivorous nonavian dinosaurs are an ideal group to test for such responses, because they dominated terrestrial ecosystems for more than 155 Myr and included the largest herbivores that ever existed. The radiation of dinosaurs was punctuated by several ecologically important events, including extinctions at the Triassic/Jurassic (Tr/J) and Jurassic/Cretaceous (J/K) boundaries, the decline of cycadophytes, and the origin of angiosperms, all of which may have had profound consequences for herbivore communities. Here we present the first analysis of morphological and biomechanical disparity for sauropodomorph and ornithischian dinosaurs in order to investigate patterns of jaw shape and function through time. We find that morphological and biomechanical mandibular disparity are decoupled: mandibular shape disparity follows taxonomic diversity, with a steady increase through the Mesozoic. By contrast, biomechanical disparity builds to a peak in the Late Jurassic that corresponds to increased functional variation among sauropods. The reduction in biomechanical disparity following this peak coincides with the J/K extinction, the associated loss of sauropod and stegosaur diversity, and the decline of cycadophytes. We find no specific correspondence between biomechanical disparity and the proliferation of angiosperms. Continual ecological and functional replacement of pre-existing taxa accounts for disparity patterns through much of the Cretaceous, with the exception of several unique groups, such as psittacosaurids that are never replaced in their biomechanical or morphological profiles.

A dinosaur missing-link? Chilesaurus and the early evolution of ornithischian dinosaurs.

The enigmatic dinosaur taxon Chilesaurus diegosuarezi was originally described as a tetanuran theropod, but this species possesses a highly unusual combination of features that could provide evidence of alternative phylogenetic positions within the clade. In order to test the relationships of Chilesaurus, we added it to a new dataset of early dinosaurs and other dinosauromorphs. Our analyses recover Chilesaurus in a novel position, as the earliest diverging member of Ornithischia, rather than a tetanuran theropod. The basal position of Chilesaurus within the clade and its suite of anatomical characters suggest that it might represent a 'transitional' taxon, bridging the morphological gap between Theropoda and Ornithischia, thereby offering potential insights into the earliest stages of ornithischian evolution, which were previously obscure. For example, our results suggest that pubic retroversion occurred prior to some of the craniodental and postcranial modifications that previously diagnosed the clade (e.g. the presence of a predentary bone and ossified tendons).

Topologically Diverse Human Membrane Proteins Partition to Liquid-Disordered Domains in Phase-Separated Lipid Vesicles.

The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease-linked proteins are insufficient to confer affinity for synthetic raft-like domains.

Modelling the climatic niche of turtles: a deep-time perspective.

Ectotherms have close physiological ties with the thermal environment; consequently, the impact of future climate change on their biogeographic distributions is of major interest. Here, we use the modern and deep-time fossil record of testudines (turtles, tortoises, and terrapins) to provide the first test of climate on the niche limits of both extant and extinct (Late Cretaceous, Maastrichtian) taxa. Ecological niche models are used to assess niche overlap in model projections for key testudine ecotypes and families. An ordination framework is applied to quantify metrics of niche change (stability, expansion, and unfilling) between the Maastrichtian and present day. Results indicate that niche stability over evolutionary timescales varies between testudine clades. Groups that originated in the Early Cretaceous show climatic niche stability, whereas those diversifying towards the end of the Cretaceous display larger niche expansion towards the modern. Temperature is the dominant driver of modern and past distributions, whereas precipitation is important for freshwater turtle ranges. Our findings demonstrate that testudines were able to occupy warmer climates than present day in the geological record. However, the projected rate and magnitude of future environmental change, in concert with other conservation threats, presents challenges for acclimation or adaptation.

Evolution of dinosaur epidermal structures.

Spectacularly preserved non-avian dinosaurs with integumentary filaments/feathers have revolutionized dinosaur studies and fostered the suggestion that the dinosaur common ancestor possessed complex integumentary structures homologous to feathers. This hypothesis has major implications for interpreting dinosaur biology, but has not been tested rigorously. Using a comprehensive database of dinosaur skin traces, we apply maximum-likelihood methods to reconstruct the phylogenetic distribution of epidermal structures and interpret their evolutionary history. Most of these analyses find no compelling evidence for the appearance of protofeathers in the dinosaur common ancestor and scales are usually recovered as the plesiomorphic state, but results are sensitive to the outgroup condition in pterosaurs. Rare occurrences of ornithischian filamentous integument might represent independent acquisitions of novel epidermal structures that are not homologous with theropod feathers.

Body mass estimates of an exceptionally complete Stegosaurus (Ornithischia: Thyreophora): comparing volumetric and linear bivariate mass estimation methods.

Body mass is a key biological variable, but difficult to assess from fossils. Various techniques exist for estimating body mass from skeletal parameters, but few studies have compared outputs from different methods. Here, we apply several mass estimation methods to an exceptionally complete skeleton of the dinosaur Stegosaurus. Applying a volumetric convex-hulling technique to a digital model of Stegosaurus, we estimate a mass of 1560 kg (95% prediction interval 1082-2256 kg) for this individual. By contrast, bivariate equations based on limb dimensions predict values between 2355 and 3751 kg and require implausible amounts of soft tissue and/or high body densities. When corrected for ontogenetic scaling, however, volumetric and linear equations are brought into close agreement. Our results raise concerns regarding the application of predictive equations to extinct taxa with no living analogues in terms of overall morphology and highlight the sensitivity of bivariate predictive equations to the ontogenetic status of the specimen. We emphasize the significance of rare, complete fossil skeletons in validating widely applied mass estimation equations based on incomplete skeletal material and stress the importance of accurately determining specimen age prior to further analyses.

Cranial biomechanics underpins high sauropod diversity in resource-poor environments.

High megaherbivore species richness is documented in both fossil and contemporary ecosystems despite their high individual energy requirements. An extreme example of this is the Late Jurassic Morrison Formation, which was dominated by sauropod dinosaurs, the largest known terrestrial vertebrates. High sauropod diversity within the resource-limited Morrison is paradoxical, but might be explicable through sophisticated resource partitioning. This hypothesis was tested through finite-element analysis of the crania of the Morrison taxa Camarasaurus and Diplodocus. Results demonstrate divergent specialization, with Camarasaurus capable of exerting and accommodating greater bite forces than Diplodocus, permitting consumption of harder food items. Analysis of craniodental biomechanical characters taken from 35 sauropod taxa demonstrates a functional dichotomy in terms of bite force, cranial robustness and occlusal relationships yielding two polyphyletic functional 'grades'. Morrison taxa are widely distributed within and between these two morphotypes, reflecting distinctive foraging specializations that formed a biomechanical basis for niche partitioning between them. This partitioning, coupled with benefits associated with large body size, would have enabled the high sauropod diversities present in the Morrison Formation. Further, this provides insight into the mechanisms responsible for supporting the high diversities of large megaherbivores observed in other Mesozoic and Cenozoic communities, particularly those occurring in resource-limited environments.