Cortical bone is highly porous and composed of an interconnecting network of vascular canals and osteocyte lacunae. Our understanding of the mechanisms coupling vascular: lacunar spatial organisation in cortical bone is poorly understood. Defining cellular cross-talk mechanisms could be key in identification of reciprocal molecular signals driving increased cortical porosity with age. Driven by the hypothesis that porosity within bone is heterogeneous and influenced by region-specific spatial cues, we utilised synchrotron X-ray computed tomography to characterise intracortical canal and osteocyte lacunae distribution, morphology and spatial arrangements in healthy and pathological murine bone. We found that the posterior region of the tibiofibular junction (TFJ) exhibited the highest levels of cortical porosity and highest canal number density compared to other regions. The volume of osteocyte lacunae positioned proximal to cortical vascular canals was highest in the posterior region. Following deletion of bone-derived VEGF, the region-specific effects on lacunar: vascular arrangements described in the wild-type TFJ were lost. Our results describe spatial diversity in osteocyte lacunae size within the bone cortex, which associates with vascular canal arrangements maintained by VEGF.

There is evidence that sorptive clays have been used since prehistory as materials to treat skin abrasions and wounds. Despite this, there is a paucity of studies that systematically address the efficacy of defined clays in improving skin wound healing. In this study, we tested the hypothesis that a well-defined synthetic smectite clay, Laponite, enhances healing in a delayed skin wound healing model. Full-thickness skin wounds were made in the back skin of db/db and wild-type male adult mice (8–10 weeks), and Laponite clay gels or controls of phosphate-buffered saline (PBS) or alginate were applied after 24 h and held in place with a semi-occlusive dressing. Although Laponite treatment did not accelerate macroscopic wound closure, it significantly improved healing quality, including re-epithelialisation, epithelial cell division, epithelial thickness and fibroblast invasion, compared with PBS- or alginate-treated db/db mice. Moreover, hair follicle anagen was stimulated in proximity to Laponite-treated wounds, but was absent in PBS- or alginate-treated wounds. Neutrophil infiltration at day 18 was also reduced. In contrast to alginate, in which VEGF improved wound healing, VEGF in Laponite showed negligible additional benefit. These data indicate a role for synthetic nanoclay gels in wound healing.

Fossils preserved on high aspect-ratio slabs of matrix ('plate-like' or 'slab' fossils with one short axis and two longer axes) include some of the most complete and scientifically significant vertebrate fossils ever discovered. These plate-like fossils are problematic to scan using conventional lab-based X-ray computed tomography (CT) for two reasons: 1) poor penetration of X-rays through the long, flat axis of the matrix slab leads to photon extinction imaging artefacts, and 2) resolution is limited by the distance required for the specimen to complete a full rotation avoiding collision with the X-ray source. One potential solution to these issues, which has yet to be thoroughly explored, is limited-angle computed tomography (LACT), a technique which involves rotating the specimen through an angle less than the full 360 degrees typically used in labbased CT. Here, we demonstrate LACT on a fossil specimen for the first time, highlighting the effects of adjusting angular sampling on scan quality. Although small angles of rotation result in significant imaging artefacts using conventional reconstruction methods (e.g., filtered back-projection), we find these artefacts are minimised at angles of rotation greater than 180 degrees. The relative benefits of LACT are dependent on the purpose of the scan and the shape, size, and material of the specimen, with potential advantages including increased resolution and reduced photon extinction artefacts. We present scenarios in which using LACT over conventional CT to scan plate-like fossils should be considered, taking advantage of a relatively simple alteration to the scanning process to improve imaging results for these problematic specimens.

Biomineralisation is essential for skeletal integrity, yet the synergistic roles of tissue non-specific alkaline phosphatase (TNAP) and PHOSPHO1 in postnatal bone mineralisation remain poorly defined. To decipher this, we generated a novel murine model in which Alpl was deleted in Prx1-expressing cells (AlplPrx1/Prx1) in mice with a global Phospho1-/- deficiency to overcome the perinatal lethality that arises upon dual global deletion. Using a multi-modal approach to spatially phenotype the limbs of these animals, we reveal mice lacking both TNAP and PHOSPHO1 exhibit a distinct lack of mineralisation and altered anatomical structure at postnatal day 1 (PN1) and 3-weeks of age. Although viable, these mice did not thrive due to their reduced size, thus further investigations were conducted on mice with a heterozygous deletion of TNAP (Alplwt/Prx1;Phospho1-/-). Although smaller than wild-types at PN1 and 3 weeks old, these mice did not display the gross limb deformations observed in the homozygous animals and the single, functioning Alpl allele rescued the loss of biomineralisation observed following dual phosphatase deletion. At 6-weeks of age, compromised epiphyses and metaphyses were only seen in AlplPrx1/Prx1 animals. Further, we found that tibial geometry and porosity was significantly altered by Phospho1 deletion (Phospho1-/-), which was compounded in the Alplwt/Prx1;Phospho1-/- mice and linked to alterations in collagen configuration, matrix mineralisation and growth plate deformities. Together, our findings establish the mechanistic framework for TNAP and PHOSPHO1 in permissive biomineralisation, providing critical insights into this fundamental process.

Bone formation during skeletal growth and repair is divergently modulated by osteoblast-derived vascular endothelial growth factor (VEGF), which contributes to the sexual dimorphism of the bone vasculature. While the extracellular matrix (ECM) provides structural and instructive cues to developing vasculature, whether the osteoblast-derived matrix contributes to this dimorphism remains unclear. Primary osteoblasts from the long bones of neonatal female and male C57BL/6J mice were cultured under basal or osteogenic conditions for compositional ECM analysis by Raman spectroscopy. Primary murine bone marrow-derived endothelial cells (BMECs) were seeded onto established osteoblast layers and maintained in heterotypic cocultures to assess contact-mediated effects of osteoblast ECM on BMEC survival and expansion. Osteoblast-derived conditioned media (CM) were used to evaluate soluble-factor contributions, with VEGF-A concentration quantified by ELISA. Raman spectroscopy of monocultured osteoblasts revealed sexually dimorphic ECM signatures independent of cellular growth profiles. Female matrices were enriched with type I collagen-associated proline and hydroxyproline and octacalcium phosphate, consistent with a matrix-dominant signature. Male matrices exhibited lower levels of collagen-associated components and instead adopted a more mineral-mature profile, reflected by CAP accumulation and an elevated mineral/matrix ratio. In heterotypic cocultures, BMEC numbers were 1.39-fold higher with male than female osteoblasts. CM treatment of BMECs did not recapitulate these effects despite higher VEGF-A release from male osteoblasts. Sex differences in osteoblast-derived ECM are linked to divergent, contact-dependent modulation of BMEC behaviour. These findings indicate that intrinsic sex differences in osteoblast matrix maturation may contribute to sex-specific regulation of the skeletal vascular niche. Defining how osteoblast-derived ECM regulates skeletal vascularisation may reveal targets for selectively modulating pathological skeletal angiogenesis in women and men. Bone is a sexually dimorphic organ, with women and men differing in bone size, strength and risk of fracture. The skeletal vasculature is essential for bone growth and repair, with bone forming osteoblast cells influencing blood vessel development through the skeletal extracellular matrix (ECM). Although the interactions between osteoblast and vascular cells are crucial for lifelong skeletal health, whether sex differences in bone structure between women and men arise from differences in osteoblast activity or sex differences in blood vessel growth remains unknown. Here, we show that female and male mouse osteoblasts deposit compositionally distinct ECMs that differentially influence vascular endothelial cell behaviour. Female osteoblasts produce a collagen-rich matrix with low mineral content. In contrast, male osteoblasts produce matrices containing less collagen and more mineral, while releasing elevated levels of the blood vessel-promoting factor, VEGF-A, compared with female osteoblasts. When placed directly onto these osteoblast layers, vascular cell growth was greater in cocultures with male than female osteoblasts and could not be reproduced by exposure to osteoblast-derived soluble factors alone. These findings identify a contact-dependent relationship through which sex differences in osteoblast ECM composition influence vascular cell behaviour in bone. Understanding how osteoblast-vascular interactions differ by sex may explain the variability in bone health, healing capacity and disease risk between women and men. Further, our approach may inform the discovery of new therapeutic targets that support bone growth and repair while targeting abnormal blood vessel growth in a sex-specific manner. Primary osteoblasts from female and male C57BL/6J mouse long bones synthesise compositionally distinct ECMs. ECM produced by female osteoblasts contains raised type I collagen-associated components and OCP, whereas the male osteoblast ECM comprises relatively lower levels of type I collagen-associated species and CAP accumulation. BMEC growth is markedly enhanced in heterotypic direct-contact cocultures with male than female osteoblasts. Male osteoblasts release higher levels of the pro-angiogenic factor, VEGF-A, than female osteoblasts. The sex-specific effects of the osteoblast ECM on BMECs are contact-dependent and are not reproduced by treatment with osteoblast-derived CM.

Medullary bone is a fast-growing, ephemeral bone tissue found inside the bone cavities of female birds. Identifying this tissue in the bones of fossil avian and non- avian dinosaurs has the potential to determine which specimens represent reproductively mature females. However, difficulties in distinguishing medullary bone from superficially similar bone pathologies has led to uncertainty as to whether some specimens previously thought to contain medullary bone instead represent sick or injured individuals. The most frequently mentioned of these pathologies is avian osteopetrosis, a virally-induced condition in birds causing bony lesions which can resemble medullary bone. Lists of criteria, primarily using two-dimensional osteohistology, have yet to form a comprehensive framework through which all medullary bone can be positively identified, and all pathology excluded. Here, we use high-resolution computed tomography (mu CT) to characterise the three-dimensional structure of medullary bone in modern birds for the first time and make comparisons to the endosteal lesions of avian osteopetrosis. We identify both qualitative and quantitative features which we suggest to be characteristic of medullary bone, including connectivity density and osteocyte lacunar orientation, and highlight conspicuously variable features which require further investigation. We find several three-dimensional which can be used to differentiate between medullary bone and avian osteopetrosis, including structural anisotropy and trabecular thickness. These three-dimensional characters can be added to the growing framework of criteria to identify medullary bone in the fossil record and thus help determine the sex of dinosaurs.

Aberrant collagen matrix production is a hallmark of many cancers, including osteosarcoma (OS), the most common primary cancer of bone which remains poorly diagnosed. Here, the phenotyping potential of second harmonic generation (SHG) microscopy has been demonstrated through label-free imaging of pathologically altered collagen matrices within clinical biopsies. This work examined SHG imaging in quantifying OS-specific collagen (type I) signatures – focused on fibre length-based parameters – across clinical biopsies. We describe a novel SHG analysis workflow, following systematic optimisation of image resolution and field of view (FOV) size to enable robust quantification of collagen fibre-length metrics in human bone and OS. This included analyses of SHG images with a FOV spanning 350 µm × 350 µm to 1400 µm × 1400 µm, with the latter enabling whole-biopsy visualisation via stitching of up to 64 regions. In normal cortical (rib) bone biopsies, average fibre lengths did not significantly differ across increasing FOV size (26.44 ± 1.75 µm, 26.34 ± 2.01 µm, 27.25 ± 2.47 µm, 28.78 ± 3.58 µm). However, analysis of the top 50th percentile of collagen fibres revealed significant differences between the smallest FOVs; 350 µm × 350 µm and 466 µm × 466 µm, versus the largest 1400 µm × 1400 µm (p = 0.03 and p = 0.04 respectively), highlighting the requirement for larger FOVs for optimal characterisation of human bone collagen. Comparison of normal bone and OS (stage IIB) biopsies, the largest FOV revealed the largest differences, with OS exhibiting significantly reduced collagen fibre lengths (female OS: 23.18 ± 0.56 µm vs. bone: 29.39 ± 2.17 µm, p < 0.001; male OS: 24.39 ± 1.32 µm vs. bone: 27.87 ± 1.05 µm, p = 0.02) versus normal bone. Subsequent analyses across OS stages (IB – IVB) showed further evidence of pathological collagen signatures amplified with OS progression. These findings demonstrate that SHG microscopy enables robust, quantitative phenotyping of human bone and osteosarcoma collagen matrices, offering new potential for improved diagnosis and disease staging. ### Competing Interest Statement The authors have declared no competing interest. Hannah's Willberry Wonder Pony, UK University of Southampton, https://ror.org/01ryk1543 Engineering and Physical Sciences Research Council, https://ror.org/0439y7842

Abstract Background Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton. Methods Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology. Results Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤ 30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. Conclusions Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.

Myeloma bone disease (MBD) affects ~90% of multiple myeloma patients, but current treatment options are suboptimal. Therefore, to successfully develop new therapies or optimize current ones, we must improve our fundamental knowledge of how myeloma affects bone microstructure and function. Here, we have investigated the osteocyte lacuno-canalicular network (LCN) in MBD, as bone porosity affects bone quality and resilience. We used the syngeneic 5TGM1-C57BL-Kalwrij and the xenograft U266-NSG models at end stage and compared them to healthy controls (naïve). Micro-computed tomography (μCT) and histomorphometry indicated the 5TGM1 and U266 models developed mild and extensive MBD, respectively, with the U266 model producing large osteolytic lesions. High-resolution synchrotron micro-CT (SR-μCT) revealed significant osteocyte lacunae changes in U266 bones but not 5TGM1, with a reduction in lacunae number and sphericity, and an increase in lacunae volume compared with naïve. Canalicular length, visualized using histological Ploton silver staining, appeared significantly shorter in 5TGM1 and U266 bones compared with naïve. Canalicular area as a proportion of the bone was also decreased by 24.2% in the U266 model. We observed significant upregulation of genes implicated in peri-lacunar remodeling (PLR), but immunohistochemistry confirmed that the osteocyte-specific protein sclerostin, a known driver of PLR, was unchanged between MBD and naïve bones. In summary, we have demonstrated evidence of PLR and altered organization of the osteocyte LCN in MBD mouse models. The next step would be to further understand the drivers and implications of PLR in MBD, and whether treatments to manipulate PLR and the LCN may improve patient outcomes.

The porous bone cortex comprises an interconnected network of intracortical vascular canals and osteocyte lacunae, embedded within the bone mineral. Increases in cortical porosity reduce bone strength and increase fracture risk. To date, our understanding of mechanisms coupling the arrangements of the vascular: lacunar network in the bone cortex is poorly understood yet it could be key in establishing regulation of cortical porosity evident with age. Using synchrotron radiation-based computed tomography we develop automated tools to characterise the 3D spatial organisation and morphology of osteocyte lacunae, and the bone vasculature at the tibiofibular junction (TFJ), defining posterior, medial, lateral, and anterior regions in male C57BL/6 mice (n = 3). We also investigate the role of osteoblast-derived VEGF in regulating the 3D spatial arrangement by conditional disruption of VEGF in osteocalcin-expressing cells (OcnVEGFKO versus WT, n = 3). Regional lacunar phenotypes were assessed by 3D distance mapping of lacunar organisation surrounding the vascular compartments, including endosteal and periosteal surfaces, or intracortical canals. Surface-associated lacunae were indistinct in size across posterior, medial, lateral and anterior regions. However, lacunae associated with intracortical canals were significantly larger exclusively within the posterior region. In the absence of VEGF, the increased lacunar volume associated with posterior intracortical canals was lost. Our results suggest that the influence of intracortical canals on lacunar volumes is spatially regulated and sensitive to locally produced growth factors such as osteoblast-derived VEGF.

Despite knowledge that sexually dimorphic mechanisms regulate bone homeostasis, sex often remains unreported and unconsidered in preclinical experimental design. Failure to report sex could lead to inappropriate generalizations of research findings and less effective translation into clinical practice. Preclinical sex bias (preferential selection of one sex) is present across other fields, including neuroscience and immunology, but remains uninvestigated in skeletal research. For context, we first summarized key literature describing sexually dimorphic bone phenotypes in mice. We then investigated sex reporting practices in skeletal research, specifically how customary it is for murine sex to be included in journal article titles or abstracts and then determined whether any bias in sex reporting exists. Because sex hormones are important regulators of bone health (gonadectomy procedures, ie, ovariectomy [OVX] and orchidectomy [ORX], are common yet typically not reported with sex), we incorporated reporting of OVX and ORX terms, representing female and male mice, respectively, into our investigations around sex bias. Between 1999 and 2020, inclusion of sex in titles or abstracts was low in murine skeletal studies (2.6%-4.06%). Reporting of OVX and ORX terms was low (1.44%-2.64%) and reporting of OVX and ORX with sex uncommon (0.4%-0.3%). When studies were combined to include both sexes and OVX (representing female) and ORX terms (representing male), a bias toward reporting of female mice was evident. However, when the terms OVX and ORX were removed, a bias toward the use of male mice was identified. Thus, studies focusing on sex hormones are biased toward female reporting with all other studies biased in reporting of male mice. We now call upon journal editors to introduce consistent guidance for transparent and accessible reporting of murine sex in skeletal research to better monitor preclinical sex bias, to diversify development of treatments for bone health, and to enable global skeletal health equity. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The digital reconstruction of neurocranial endocasts has elucidated the gross brain structure and potential ecological attributes of many fossil taxa, including Irritator , a spinosaurine spinosaurid from the “mid” Cretaceous (Aptian) of Brazil. With unexceptional hearing capabilities, this taxon was inferred to integrate rapid and controlled pitch‐down movements of the head that perhaps aided in the predation of small and agile prey such as fish. However, the neuroanatomy of baryonychine spinosaurids remains to be described, and potentially informs on the condition of early spinosaurids. Using micro‐computed tomographic scanning (μCT), we reconstruct the braincase endocasts of Baryonyx walkeri and Ceratosuchops inferodios from the Wealden Supergroup (Lower Cretaceous) of England. We show that the gross endocranial morphology is similar to other non‐maniraptoriform theropods, and corroborates previous observations of overall endocranial conservatism amongst more basal theropods. Several differences of unknown taxonomic utility are noted between the pair. Baryonychine neurosensory capabilities include low‐frequency hearing and unexceptional olfaction, whilst the differing morphology of the floccular lobe tentatively suggests less developed gaze stabilisation mechanisms relative to spinosaurines. Given the morphological similarities observed with other basal tetanurans, baryonychines likely possessed comparable behavioural sophistication, suggesting that the transition from terrestrial hypercarnivorous ancestors to semi‐aquatic “generalists” during the evolution of Spinosauridae did not require substantial modification of the brain and sensory systems.

We present a topological method for the detection and quantification of bone microstructure from non-linear microscopy images. Specifically, we analyse second harmonic generation (SHG) and two photon excited autofluorescence (TPaF) images of bone tissue which capture the distribution of matrix (fibrillar collagen) structure and autofluorescent molecules, respectively. Using persistent homology statistics with a signed Euclidean distance transform filtration on binary patches of images, we are able to quantify the number, size, distribution, and crowding of holes within and across samples imaged at the microscale. We apply our methodology to a previously characterized murine model of skeletal pathology whereby vascular endothelial growth factor expression was deleted in osteocalcin-expressing cells (OcnVEGFKO) presenting increased cortical porosity, compared to wild type (WT) littermate controls. We show significant differences in topological statistics between the OcnVEGFKO and WT groups and, when classifying the males, or females respectively, into OcnVEGFKO or WT groups, we obtain high prediction accuracies of 98.7% (74.2%) and 77.8% (65.8%) respectively for SHG (TPaF) images. The persistence statistics that we use are fully interpretable, can highlight regions of abnormality within an image and identify features at different spatial scales.

Spinosaurids are among the most distinctive and yet poorly-known of large-bodied theropod dinosaurs, a situation exacerbated by their mostly fragmentary fossil record and competing views regarding their palaeobiology. Here, we report two new Early Cretaceous spinosaurid specimens from the Wessex Formation (Barremian) of the Isle of Wight. Large-scale phylogenetic analyses using parsimony and Bayesian techniques recover the pair in a new clade within Baryonychinae that also includes the hypodigm of the African spinosaurid Suchomimus . Both specimens represent distinct and novel taxa, herein named Ceratosuchops inferodios gen. et sp. nov. and Riparovenator milnerae gen. et sp. nov. A palaeogeographic reconstruction suggests a European origin for Spinosauridae, with at least two dispersal events into Africa. These new finds provide welcome information on poorly sampled areas of spinosaurid anatomy, suggest that sympatry was present and potentially common in baryonychines and spinosaurids as a whole, and contribute to updated palaeobiogeographic reconstructions for the clade.

Collagen assembly during development is essential for successful matrix mineralisation, which determines bone quality and mechanocompetence. However, the biochemical and structural perturbations that drive pathological skeletal collagen configuration remain unclear. Deletion of vascular endothelial growth factor (VEGF; also known as VEGFA) in bone-forming osteoblasts (OBs) induces sex-specific alterations in extracellular matrix (ECM) conformation and mineralisation coupled to vascular changes, which are augmented in males. Whether this phenotypic dimorphism arises as a result of the divergent control of ECM composition and its subsequent arrangement is unknown and is the focus of this study. Herein, we used murine osteocalcin-specific Vegf knockout (OcnVEGFKO) and performed ex vivo multiscale analysis at the tibiofibular junction of both sexes. Label-free and non-destructive polarisation-resolved second-harmonic generation ( p-SHG) microscopy revealed a reduction in collagen fibre number in males following the loss of VEGF, complemented by observable defects in matrix organisation by backscattered electron scanning electron microscopy. This was accompanied by localised divergence in collagen orientation, determined by p-SHG anisotropy measurements, as a result of OcnVEGFKO. Raman spectroscopy confirmed that the effect on collagen was linked to molecular dimorphic VEGF effects on collagen-specific proline and hydroxyproline, and collagen intra-strand stability, in addition to matrix carbonation and mineralisation. Vegf deletion in male and female murine OB cultures in vitro further highlighted divergence in genes regulating local ECM structure, including Adamts2, Spp1, Mmp9 and Lama1. Our results demonstrate the utility of macromolecular imaging and spectroscopic modalities for the detection of collagen arrangement and ECM composition in pathological bone. Linking the sex-specific genetic regulators to matrix signatures could be important for treatment of dimorphic bone disorders that clinically manifest in pathological nano- and macro-level disorganisation. This article has an associated First Person interview with the first author of the paper.

Synthetic clays are promising biomaterials for delivery of therapeutic molecules in regenerative medicine. However, before their use can be translated into clinical applications, their safety must be assessed in human volunteers. The aim of this study was to test the hypothesis that a synthetic nanoclay (LAPONITE) does not cause irritation to the human skin. To achieve this, a nanoclay gel at two different concentrations (1.5 and 3% w/v) was applied on the forearm of healthy volunteers for 24 h. 1% sodium lauryl sulfate (SLS) and 3% (w/v) polyacrylic acid were used as the positive and negative controls, respectively. The compromise in the skin barrier function was measured by trans-epidermal water loss (TEWL), erythema by spectroscopic measurements, and skin inflammatory biomarkers (IL-1α and IL-1RA) by the enzyme-linked immunosorbent assay. We found that the nanoclay caused no prolonged increase in TEWL, erythema, or induction of inflammatory cytokines. This was in contrast to 1% SLS, a known irritant, which induced significant increases in both skin erythema and TEWL. We conclude that the nanoclay is not an irritant and is thus suitable for therapeutic interventions at the skin surface.

A series of axial elements from the Aptian Ferruginous Sands Formation of the Lower Greensand Group, discovered on the foreshore near Knock Cliff on the Isle of Wight, UK are (bar some isolated teeth and fragmentary postcranial material from the Cenomanian Cambridge Greensand) the youngest non‐avian theropod remains reported from the British Mesozoic. These specimens have the potential to shed light on a poorly known section of the European dinosaur record. Consistency in size, appearance and adhering matrix indicates that the vertebrae belong to the same individual. This was a mid‐sized tetanuran, the presence of several diagnostic characters indicating that it should be recognized as a new taxon, herein named Vectaerovenator inopinatus. The cervical and dorsal vertebrae are camerate and highly pneumatic. Tetanuran features include opisthocoelous cervicals and pneumatic foramina located within fossae; however, assigning this specimen to a specific clade is problematic. Within Tetanurae, Vectaerovenator possesses axial structures and homoplastic features seen in megalosauroids, carcharodontosaurians and certain coelurosaurs. Not only is Vectaerovenator one of the UK's youngest non‐bird dinosaurs, and one of few valid British Greensand taxa, it is also the first diagnosable theropod taxon to be named from Aptian deposits of Europe.

GENERAL COMMENTARY article Front. Endocrinol., 25 June 2020 | https://doi.org/10.3389/fendo.2020.00419