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Pathophysiological conditions can modify the skeletal chemical concentration. This study analyzes the elemental composition in two anatomical regions from dry femoral bone using a portable X-Ray Fluorescence (pXRF) and evaluates its impact in the bone mineral density (BMD). The left femora of 97 female skeletons (21–95 years old individuals) from the Coimbra Identified Skeletal Collection were studied. Diagenetic biases were discarded at the outset and BMD was determined with Dual-energy X-ray absorptiometry. Chemical measurements were performed at the midpoint of the femoral neck and at the midshaft using a pXRF device, and comparisons were made considering the age and the BMD values. Only elements with a Technical Measurement Error ≤ 5% were selected: P, S, Ca, Fe, Zn, As, Sr, Pb and the Ca/P ratio. Statistically significant differences were found between regions, with higher concentrations of P, Ca, Zn and S at the midshaft, and the Ca/P ratio at the femoral neck. The concentration of P is higher in individuals, This study was supported by the ERASMUS+ internship [SZ] performed in the Research Centre for Anthropology and Health (CIAS: PEstOE/SADG/UI0283/2020) at the University of Coimbra and the FCT-Fellowship SFRH/BD/115691/2016 [AMC]. FCT-Fellowship SFRH/BD/115691/2016 [AMC], Erasmus + Program [SZ].

Pathophysiological conditions can modify the skeletal chemical concentration. This study analyzes the elemental composition in two anatomical regions from dry femoral bone using a portable X-Ray Fluorescence (pXRF) and evaluates its impact in the bone mineral density (BMD). The left femora of 97 female skeletons (21-95 years old individuals) from the Coimbra Identified Skeletal Collection were studied. Diagenetic biases were discarded at the outset and BMD was determined with Dual-energy X-ray absorptiometry. Chemical measurements were performed at the midpoint of the femoral neck and at the midshaft using a pXRF device, and comparisons were made considering the age and the BMD values. Only elements with a Technical Measurement Error ≤ 5% were selected: P, S, Ca, Fe, Zn, As, Sr, Pb and the Ca/P ratio. Statistically significant differences were found between regions, with higher concentrations of P, Ca, Zn and S at the midshaft, and the Ca/P ratio at the femoral neck. The concentration of P is higher in individuals 50 years, while S and Ca/P ratio increase in individuals ≥ 50 years. The decrease of P with age can be simultaneously related to the decline of its concentration in osteoporosis. Decreased BMD is also associated with higher levels of S and Pb. Osteoporosis enhances the absorption of osteolytic elements in specific locations. This fast and non-destructive technique has proved effective for the comprehension of chemical changes related to bone mass loss. This study highlights the potential of identified skeletal collections to improve the knowledge about bone fragility.

Objective To improve the differential diagnosis of osteopoikilosis in past populations using a clinical case as an example of this rare condition. Materials A patient referred to our Genetic Service with suspected Buschke Ollendorff Syndrome after finding a connective nevus. Methods Radiological images from different body regions were accompanied by a genetic study using next-generation sequencing. Results Small circular-to-ellipsoid sclerotic lesions were found in the epiphysis and metaphysis of long bones, as well as in the pelvis. These lesions were bilaterally distributed and with well-defined margins, compatible with the characteristics of Buschke Ollendorff Syndrome, bone manifestation osteopoikilosis. A heterozygous mutation on LEMD3 (NM_001167614:c.1918 + 1G > C) was identified by next-generation sequencing. Based on this confirmed case, we have discussed the most probable causes of similar bone lesions found in the archaeological record. Conclusion It has been demonstrated how a current case of a rare disease can provide useful tools to improve the differential diagnosis of this disease in ancient skeletons. Significance This work underlines the great need for multidisciplinary platforms that integrates clinical research into paleopathology in order to successfully address the study of rare diseases from the past. Limitations Since OPK is only detected by X-rays, suspected cases of this bone lesion will only be identified when radiographs are taken for other purposes. Suggestions for further research Retrospective and large-scale studies of radiographs from other research in past populations.

VertebrateHoxgenes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that theHoxCgene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of theHoxCcluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function ofHoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two ectodermal, mammalian-specific enhancers located upstream of theHoxCgene cluster, which act synergistically to regulateHoxcgene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation ofHoxcgenes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.Significance StatementIn this study, we report a unique and necessary function for theHoxCgene cluster in the development of some ectodermal organs, as illustrated both by the hair and nail phenotype displayed by mice lacking theHoxc13function and by the congenital anonychia (absence of nails) in fullHoxCcluster mutants. We show thatHoxcgenes are activated in a colinear manner in the embryonic limb ectoderm and are subsequently transcribed in developing nails and hairs. We identify two mammalian-specific enhancers located upstream of theHoxCcluster with and exclusive ectodermal specificity. Individual or combined enhancer deletions suggest that they act in combination to raise the transcription level of severalHoxcgenes during hairs and nails development.

© 2020 the Author(s)., Vertebrate Hox genes are critical for the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here, we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia), a condition stronger than the previously reported loss of function of Hoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two mammalian-specific ectodermal enhancers located upstream of the HoxC gene cluster, which together regulate Hoxc gene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation of Hoxc genes in the ectoderm, suggesting that these two enhancers may have evolved along with the mammalian taxon to provide the level of HOXC proteins necessary for the full development of hair and nail., This work was supported by funds from the Ecole Polytechnique Fédérale (Lausanne), the University of Geneva and the Swiss National Research Fund (310030B_138662), and the European Research Council grants RegulHox (588029) to D.D., and by the Spanish Ministry of Science and Innovation (Grant BFU2017-88265-P) to M.A.R.