The oldest three-dimensionally preserved vertebrate neurocranium.

The neurocranium is an integral part of the vertebrate head, itself a major evolutionary innovation1,2. However, its early history remains poorly understood, with great dissimilarity in form between the two living vertebrate groups: gnathostomes (jawed vertebrates) and cyclostomes (hagfishes and lampreys)2,3. The 100 Myr gap separating the Cambrian appearance of vertebrates4-6 from the earliest three-dimensionally preserved vertebrate neurocrania7 further obscures the origins of modern states. Here we use computed tomography to describe the cranial anatomy of an Ordovician stem-group gnathostome: Eriptychius americanus from the Harding Sandstone of Colorado, USA8. A fossilized head of Eriptychius preserves a symmetrical set of cartilages that we interpret as the preorbital neurocranium, enclosing the fronts of laterally placed orbits, terminally located mouth, olfactory bulbs and pineal organ. This suggests that, in the earliest gnathostomes, the neurocranium filled out the space between the dermal skeleton and brain, like in galeaspids, osteostracans and placoderms and unlike in cyclostomes2. However, these cartilages are not fused into a single neurocranial unit, suggesting that this is a derived gnathostome trait. Eriptychius fills a major temporal and phylogenetic gap in our understanding of the evolution of the gnathostome head, revealing a neurocranium with an anatomy unlike that of any previously described vertebrate.

The three-dimensionally articulated oral apparatus of a Devonian heterostracan sheds light on feeding in Palaeozoic jawless fishes.

Attempts to explain the origin and diversification of vertebrates have commonly invoked the evolution of feeding ecology, contrasting the passive suspension feeding of invertebrate chordates and larval lampreys with active predation in living jawed vertebrates. Of the extinct jawless vertebrates that phylogenetically intercalate these living groups, the feeding apparatus is well-preserved only in the early diverging stem-gnathostome heterostracans. However, its anatomy remains poorly understood. Here, we use X-ray microtomography to characterize the feeding apparatus of the pteraspid heterostracan Rhinopteraspis dunensis (Roemer, 1855). The apparatus is composed of 13 plates arranged approximately bilaterally, most of which articulate from the postoral plate. Our reconstruction shows that the oral plates were capable of rotating around the transverse axis, but likely with limited movement. It also suggests the nasohypophyseal organs opened internally, into the pharynx. The functional morphology of the apparatus in Rhinopteraspis precludes all proposed interpretations of feeding except for suspension/deposit feeding and we interpret the apparatus as having served primarily to moderate the oral gape. This is consistent with evidence that at least some early jawless gnathostomes were suspension feeders and runs contrary to macroecological scenarios that envisage early vertebrate evolution as characterized by a directional trend towards increasingly active food acquisition.

The role of miniaturization in the evolution of the mammalian jaw and middle ear.

The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million years1,2. In particular, the transformation of the mandible into a single tooth-bearing bone and the emergence of a novel jaw joint-while incorporating some of the ancestral jaw bones into the mammalian middle ear-is often cited as a classic example of the repurposing of morphological structures3,4. Although it is remarkably well-documented in the fossil record, the evolution of the mammalian jaw still poses the paradox of how the bones of the ancestral jaw joint could function both as a joint hinge for powerful load-bearing mastication and as a mandibular middle ear that was delicate enough for hearing. Here we use digital reconstructions, computational modelling and biomechanical analyses to demonstrate that the miniaturization of the early mammalian jaw was the primary driver for the transformation of the jaw joint. We show that there is no evidence for a concurrent reduction in jaw-joint stress and increase in bite force in key non-mammaliaform taxa in the cynodont-mammaliaform transition, as previously thought5-8. Although a shift in the recruitment of the jaw musculature occurred during the evolution of modern mammals, the optimization of mandibular function to increase bite force while reducing joint loads did not occur until after the emergence of the neomorphic mammalian jaw joint. This suggests that miniaturization provided a selective regime for the evolution of the mammalian jaw joint, followed by the integration of the postdentary bones into the mammalian middle ear.

Different, but the same: Inferring the hunting behaviour of the hypercarnivorous bush dog (Speothos venaticus) through finite element analysis.

Cerdocyonina is a clade composed by the South-American canids in which the bush dog (Speothos venaticus) is one of the most elusive species. Known for its unique morphology within the group, this small, bear-like faced canid is the only member of the clade adapted to hypercarnivory, an almost exclusively meat-based diet currently present only in usually large, pack-hunting canids such as the grey wolf (Canis lupus). However, much of the biology of the bush dog is poorly understood, and inferences about its ecology, hunting strategies and diet are usually based on observation of captive individuals and anecdotal records, with reduced quantitative data to offer support. Here, we investigated the craniomandibular functional morphology of the bush dog through finite element analysis (FEA). FEA was employed to model the biting behaviour and to create extrinsic and intrinsic functional scenarios with different loads, corresponding to different bites used to subdue and process the prey. For comparison, the same modelling was applied to the skull of a grey wolf and a grey fox (Urocyon cinereoargenteus). Our analysis showed that the bush dog's responses to loading are more similar to the wolf's than to the fox's in most scenarios, suggesting a convergent craniomandibular functional morphology between these two hypercarnivorous species, despite their distinct phylogenetic positions and body sizes. Differences between the three taxa are noteworthy and suggested to be related to the size of the usual prey. The modelled bite force for the bush dog is relatively strong, about half of that estimated for the wolf and about 40% stronger than the fox's bite. The results strengthen with quantitative data the inferences of the bush dog as a pack-hunting predator with prey size similar to its own, such as large rodents and armadillos, being specialised in subduing and killing its prey using multiple bites. Its similarity to the wolf also confirms anecdotal accounts of predation on mammals that are much larger than itself, such as peccaries and tapirs. These data highlight the ecological specialisation of this small canid in a continent where large, pack-hunting canids are absent.

Three-dimensional modelling, disparity and ecology of the first Cambrian apex predators.

Radiodonts evolved to become the largest nektonic predators in the Cambrian period, persisting into the Ordovician and perhaps up until the Devonian period. They used a pair of large frontal appendages together with a radial mouth apparatus to capture and manipulate their prey, and had evolved a range of species with distinct appendage morphologies by the Early Cambrian (approx. 521 Ma). However, since their discovery, there has been a lack of understanding about their basic functional anatomy, and thus their ecology. To explore radiodont modes of feeding, we have digitally modelled different appendage morphologies represented by Anomalocaris canadensis, Hurdia victoria, Peytoia nathorsti, Amplectobelua stephenensis and Cambroraster falcatus from the Burgess Shale. Our results corroborate ideas that there was probably a significant (functional and hence behavioural) diversity among different radiodont species with adaptations for feeding on differently sized prey (0.07 cm up to 10 cm). We argue here that Cambroraster falcatus appendages were suited for feeding on suspended particles rather than filtering sediment. Given the limited dexterity and lack of accessory feeding appendages as seen in modern arthropods, feeding must have been inefficient and 'messy', which may explain their subsequent replacement by crown-group arthropods, cephalopods and jawed vertebrates.

Morphological convergence obscures functional diversity in sabre-toothed carnivores.

The acquisition of elongated, sabre-like canines in multiple vertebrate clades during the last 265 Myr represents a remarkable example for convergent evolution. Due to striking superficial similarities in the cranial skeleton, the same or similar skull and jaw functions have been inferred for sabre-toothed species and interpreted as an adaptation to subdue large-bodied prey. However, although some sabre-tooth lineages have been classified into different ecomorphs (dirk-tooths and scimitar-tooths) the functional diversity within and between groups and the evolutionary paths leading to these specializations are unknown. Here, we use a suite of biomechanical simulations to analyse key functional parameters (mandibular gape angle, bending strength, bite force) to compare the functional performance of different groups and to quantify evolutionary rates across sabre-tooth vertebrates. Our results demonstrate a remarkably high functional diversity between sabre-tooth lineages and that different cranial function and prey killing strategies evolved within clades. Moreover, different biomechanical adaptations in coexisting sabre-tooth species further suggest that this functional diversity was at least partially driven by niche partitioning.

A unique predator in a unique ecosystem: modelling the apex predator within a Late Cretaceous crocodyliform-dominated fauna from Brazil.

Theropod dinosaurs were relatively scarce in the Late Cretaceous ecosystems of southeast Brazil. Instead, hypercarnivorous crocodyliforms known as baurusuchids were abundant and probably occupied the ecological role of apex predators. Baurusuchids exhibited a series of morphological adaptations hypothesized to be associated with this ecological role, but quantitative biomechanical analyses of their morphology have so far been lacking. Here, we employ a biomechanical modelling approach, applying finite element analysis (FEA) to models of the skull and mandibles of a baurusuchid specimen. This allows us to characterize the craniomandibular apparatus of baurusuchids, as well as to compare the functional morphology of the group with that of other archosaurian carnivores, such as theropods and crocodylians. Our results support the ecological role of baurusuchids as specialized apex predators in the continental Late Cretaceous ecosystems of South America. With a relatively weak bite force (~600 N), the predation strategies of baurusuchids likely relied on other morphological specializations, such as ziphodont dentition and strong cervical musculature. Comparative assessments of the stress distribution and magnitude of scaled models of other predators (the theropod Allosaurus fragilis and the living crocodylian Alligator mississippiensis) consistently show different responses to loadings under the same functional scenarios, suggesting distinct predatory behaviors for these animals. The unique selective pressures in the arid to semi-arid Late Cretaceous ecosystems of southeast Brazil, which were dominated by crocodyliforms, possibly drove the emergence and evolution of the biomechanical features seen in baurusuchids, which are distinct from those previously reported for other predatory taxa.

Effects of body plan evolution on the hydrodynamic drag and energy requirements of swimming in ichthyosaurs.

Ichthyosaurs are an extinct group of fully marine tetrapods that were well adapted to aquatic locomotion. During their approximately 160 Myr existence, they evolved from elongate and serpentine forms into stockier, fish-like animals, convergent with sharks and dolphins. Here, we use computational fluid dynamics (CFD) to quantify the impact of this transition on the energy demands of ichthyosaur swimming for the first time. We run computational simulations of water flow using three-dimensional digital models of nine ichthyosaurs and an extant functional analogue, a bottlenose dolphin, providing the first quantitative evaluation of ichthyosaur hydrodynamics across phylogeny. Our results show that morphology did not have a major effect on the drag coefficient or the energy cost of steady swimming through geological time. We show that even the early ichthyosaurs produced low levels of drag for a given volume, comparable to those of a modern dolphin, and that deep 'torpedo-shaped' bodies did not reduce the cost of locomotion. Our analysis also provides important insight into the choice of scaling parameters for CFD applied to swimming mechanics, and underlines the great influence of body size evolution on ichthyosaur locomotion. A combination of large bodies and efficient swimming modes lowered the cost of steady swimming as ichthyosaurs became increasingly adapted to a pelagic existence.

[Skin changes as a characteristic of internal diseases]. / Hautveränderungen als Merkmal internistischer Erkrankungen.

Skin changes as a characteristic of internal diseases Abstract. Numerous skin changes are of great importance, as they can be groundbreaking for basic internal diseases or indicate associated complications or side effects of therapies. The early detection of such marker manifestations allows immediate action to prevent potentially serious consequences. For example, specific skin changes in limited forms of collagenosis may not only be diagnostically significant, but also prognostically significant, which allows gentler therapies if the course of the disease is more favourable. The most important prerequisite for a correct diagnosis of cutaneous lesions is a careful and complete skin status with additional consideration of the adjacent mucous membranes and skin appendages. In a first step, the primary anatomical site, morphology and lesion location should be identified and then the distribution assessed. This article describes more frequent skin manifestations in diseases of different organ systems (with the exception of infections, less frequent metabolic disorders and drug side effects).

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.

Palate anatomy and morphofunctional aspects of interpterygoid vacuities in temnospondyl cranial evolution.

Temnospondyls were the morphologically and taxonomically most diverse group of early tetrapods with a near-global distribution during the Palaeozoic and Mesozoic. Members of this group occupied a range of different habitats (aquatic, amphibious, terrestrial), reflected by large morphological disparity of the cranium throughout their evolutionary history. A diagnostic feature of temnospondyls is the presence of an open palate with large interpterygoid vacuities, in contrast to the closed palate of most other early tetrapods and their fish-like relatives. Although the function of the interpterygoid vacuities has been discussed in the past, no quantitative studies have been performed to assess their biomechanical significance. Here, we applied finite element analysis, to test the possibility that the interpterygoid vacuities served for stress distribution during contraction of the jaw closing musculature. Different original and theoretical skull models, in which the vacuities differed in size or were completely absent, were compared for their mechanical performance. Our results demonstrate that palatal morphology played a considerable role in cranial biomechanics of temnospondyls. The presence of large cranial vacuities were found to offer the dual benefit of providing additional muscle attachment areas and allowing for more effective force transmission and thus an increase in bite force without compromising cranial stability.

Edentulism, beaks, and biomechanical innovations in the evolution of theropod dinosaurs.

Maniraptoriformes, the speciose group of derived theropod dinosaurs that ultimately gave rise to modern birds, display a diverse and remarkable suite of skeletal adaptations. Apart from the evolution of flight, a large-scale change in dietary behavior appears to have been one of the main triggers for specializations in the bauplan of these derived theropods. Among the different skeletal specializations, partial or even complete edentulism and the development of keratinous beaks form a recurring and persistent trend in from the evolution of derived nonavian dinosaurs. Therizinosauria is an enigmatic maniraptoriform clade, whose members display these and other osteological characters thought to be correlated with the shift from carnivory to herbivory. This makes therizinosaurians prime candidates to assess the functional significance of these morphological characters. Based on a highly detailed biomechanical model of Erlikosaurus andrewsi, a therizinosaurid from the Upper Cretaceous of Mongolia, different morphological configurations incorporating soft-tissue structures, such as a keratinous rhamphotheca, are evaluated for their biomechanical performance. Our results indicate that the development of beaks and the presence of a keratinous rhamphotheca would have helped to dissipate stress and strain, making the rostral part of the skull less susceptible to bending and displacement, and this benefit may extend to other vertebrate clades that possess rhamphothecae. Keratinous beaks, paralleled by edentulism, thus represent an evolutionary innovation developed early in derived theropods to enhance cranial stability, distinct to postulated mass-saving benefits associated with the origin of flight.

Use of Treponema pallidum PCR in testing of ulcers for diagnosis of primary syphilis.

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.

Comparison of Diagnostic Accuracy of PCR Targeting the 47-Kilodalton Protein Membrane Gene of Treponema pallidum and PCR Targeting the DNA Polymerase I Gene: Systematic Review and Meta-analysis.

Treponema pallidum PCR (Tp-PCR) testing now is recommended as a valid tool for the diagnosis of primary or secondary syphilis. The objectives were to systematically review and determine the optimal specific target gene to be used for Tp-PCR. Comparisons of the performance of the two main targets are tpp47 and polA genes were done using meta-analysis. Three electronic bibliographic databases, representing abstract books from five conferences specialized in infectious diseases from January 1990 to March 2015, were searched. Search keywords included ("syphilis" OR "Treponema pallidum" OR "neurosyphilis") AND ("PCR" OR "PCR" OR "molecular amplification"). We included diagnostic studies assessing the performance of Tp-PCR targeting tpp47 (tpp47-Tp-PCR) or the polA gene (polA-Tp-PCR) in ulcers from early syphilis. All studies were assessed against quality criteria using the QUADAS-2 tool. Of 37 studies identified, 62.2% were judged at low risk of bias or applicability. Most used the U.S. Centers for Disease Control and Prevention (CDC) case definitions for primary or secondary (early) syphilis (89.2%; n = 33); 15 (40.5%) used darkfield microscopy (DFM). We did not find differences in sensitivity and specificity between the two Tp-PCR methods in the subgroup of studies using adequate reference tests. Among studies using DFM as the reference test, sensitivities were 79.8% (95% confidence intervals [CI], 72.7 to 85.4%) and 71.4% (46.0 to 88.0%) for tpp47-Tp-PCR and polA-Tp-PCR (P = 0.217), respectively; respective specificities were 95.3% (93.5 to 96.6%) and 93.7% (91.8 to 95.2%) (P = 0.304). Our findings suggest that the two Tp-PCR methods have similar accuracy and could be used interchangeably.

Performance of the 47-kilodalton membrane protein versus DNA polymerase I genes for detection of Treponema pallidum by PCR in ulcers.

Treponema pallidum PCR (Tp-PCR) is a direct diagnostic method for primary and secondary syphilis, but there is no recommendation regarding the best choice of target gene. In this study, we sequentially tested 272 specimens from patients with sexually transmitted ulcers using Tp-PCR targeting the tpp47 and then polA genes. The two methods showed similar accuracies and an almost-perfect agreement.

Tinea genitalis: a new entity of sexually transmitted infection? Case series and review of the literature.

OBJECTIVE: Investigation on recent cases of tinea genitalis after travelling to South East Asia. METHODS: Patients with tinea in the genital region, which emerged after sex in South East Asia, underwent further assessment including microscopy, cultures and DNA analyses. RESULTS: The case series includes seven patients. In six patients, Trichophyton interdigitale (former Trichophyton mentagrophytes) was detected. Three patients suffered from a severe inflammatory reaction of the soft tissue and two of them needed hospitalisation due to severe pain. In four patients, cicatrising healing was noticed. Five patients were declared incapacitated for work. CONCLUSIONS: Sexual activity should be considered as a potentially important and previously underappreciated means of transmission of T. interdigitale. To avoid irreversible scarring alopecia, prompt initiation of antifungal treatment is essential and adequate isolation and identification of the pathogen is mandatory.

Morphological and functional diversity in therizinosaur claws and the implications for theropod claw evolution.

Therizinosaurs are a group of herbivorous theropod dinosaurs from the Cretaceous of North America and Asia, best known for their iconically large and elongate manual claws. However, among Therizinosauria, ungual morphology is highly variable, reflecting a general trend found in derived theropod dinosaurs (Maniraptoriformes). A combined approach of shape analysis to characterize changes in manual ungual morphology across theropods and finite-element analysis to assess the biomechanical properties of different ungual shapes in therizinosaurs reveals a functional diversity related to ungual morphology. While some therizinosaur taxa used their claws in a generalist fashion, other taxa were functionally adapted to use the claws as grasping hooks during foraging. Results further indicate that maniraptoriform dinosaurs deviated from the plesiomorphic theropod ungual morphology resulting in increased functional diversity. This trend parallels modifications of the cranial skeleton in derived theropods in response to dietary adaptation, suggesting that dietary diversification was a major driver for morphological and functional disparity in theropod evolution.

Digital dissection - using contrast-enhanced computed tomography scanning to elucidate hard- and soft-tissue anatomy in the Common Buzzard Buteo buteo.

Gross dissection has a long history as a tool for the study of human or animal soft- and hard-tissue anatomy. However, apart from being a time-consuming and invasive method, dissection is often unsuitable for very small specimens and often cannot capture spatial relationships of the individual soft-tissue structures. The handful of comprehensive studies on avian anatomy using traditional dissection techniques focus nearly exclusively on domestic birds, whereas raptorial birds, and in particular their cranial soft tissues, are essentially absent from the literature. Here, we digitally dissect, identify, and document the soft-tissue anatomy of the Common Buzzard (Buteo buteo) in detail, using the new approach of contrast-enhanced computed tomography using Lugol's iodine. The architecture of different muscle systems (adductor, depressor, ocular, hyoid, neck musculature), neurovascular, and other soft-tissue structures is three-dimensionally visualised and described in unprecedented detail. The three-dimensional model is further presented as an interactive PDF to facilitate the dissemination and accessibility of anatomical data. Due to the digital nature of the data derived from the computed tomography scanning and segmentation processes, these methods hold the potential for further computational analyses beyond descriptive and illustrative proposes.

Primary cutaneous follicle center lymphoma with diffuse CD30 expression: a report of 4 cases of a rare variant.

BACKGROUND: CD30 is expressed in aggressive and Epstein-Barr virus-associated forms of B-cell non-Hodgkin lymphomas, but is rarely expressed by the majority of tumor cells in primary cutaneous B-cell lymphomas (CBCLs). The expression of CD30 in CBCLs may be at risk for misinterpretation as an unequivocal indicator of a highly aggressive form of the disease. OBJECTIVE: We report 4 cases of low malignant primary cutaneous follicle center lymphoma (PCFCL) with diffuse and strong expression of CD30 by the majority of neoplastic cells. RESULTS: The patients included 3 men and 1 woman with tumors on the scalp (3 patients) and chest wall (1 patient). The histologic examinations revealed a mixed, diffuse, and follicular growth pattern with CD20(+), bcl-6(+), and bcl-2(-) tumor cells. Seventy percent to 90% of the tumor cells expressed CD30. Clonal rearrangement of immunoglobulin heavy chain genes was found in 1 of 4 cases. None of the 3 cases yielded positivity for Epstein-Barr virus RNA. LIMITATIONS: The study is limited by the small number of patients. CONCLUSIONS: This rare variant of CD30(+) PCFCL needs be distinguished from CD30(+) aggressive B-cell lymphomas. CD30 in this variant of CBCLs may serve as a therapeutic target for anti-CD30 antibody-based strategies.

BEYOND THE PRINT-VIRTUAL PALEONTOLOGY IN SCIENCE PUBLISHING, OUTREACH, AND EDUCATION.

Virtual paleontology unites a variety of computational techniques and methods for the visualization and analysis of fossils. Due to their great potential and increasing availability, these methods have become immensely popular in the last decade. However, communicating the wealth of digital information and results produced by the various techniques is still exacerbated by traditional methods of publication. Transferring and processing three-dimensional information, such as interactive models or animations, into scientific publications still poses a challenge. Here, we present different methods and applications to communicate digital data in academia, outreach and education. Three-dimensional PDFs, QR codes, anaglyph stereo imaging, and rapid prototyping-methods routinely used in the engineering, entertainment, or medical industries-are outlined and evaluated for their potential in science publishing and public engagement. Although limitations remain, these are simple, mostly cost-effective, and powerful tools to create novel and innovative resources for education, public engagement, or outreach.