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 | 1125 BARKER et al.
The porous bone cortex comprises of a complex interconnecting network of intracortical vascular canals and osteocyte lacunae embedded within the bone mineral, with increases in cortical porosity reducing bone strength and increasing fracture risk. To date, our understanding of mechanisms coupling spatial vascular: lacunar network arrangements in the bone cortex is poorly understood yet it could be key in establishing cellular contributions to alterations cortical porosity evident with age. Using synchrotron radiation-based computed tomography we developed automated tools to characterise 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 C57BL6 mice (n = 3). We also investigated a role for 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 the lacunae organisation surrounding the vascular compartments within cortical bone including endosteal/periosteal surfaces or intracortical canals. Endosteal/periosteal surface associated lacunae were indistinct in size across posterior, medial, lateral and anterior regions. However, lacunae associated with intracortical canals were significantly larger but only 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 are spatially regulated and sensitive to locally produced growth factors such as osteoblast-derived VEGF.
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