Bone histomorphometric measures of physical activity in children from Medieval England

Objectives: Histomorphometric studies show consistent links between physical activity patterns and the microstructure underlying the size and shape of bone. Here we adopt a combined bone approach to explore variation in microstructure of ribs and humeri related to physical activity and historical records of manual labor in skeletal samples of children (n=175) from medieval England. The humerus reflects greater biomechanically induced microstructural variation than the rib which is used here as a control. Variation in microstructure is sought between regions in England (Canterbury, York, Newcastle), and between high- and low-status children from Canterbury. Materials and Methods: Thin-sections were prepared from the humerus or rib and features of bone remodeling were recorded using high-resolution microscopy and image analysis software. Results: The density and size of secondary osteons in the humerus differed significantly in children from Canterbury when compared to those from York and Newcastle. Amongst the older children, secondary osteon circularity and diameter differed significantly between higher and lower status children. Discussion: By applying bone remodeling principles to the histomorphometric data we infer that medieval children in Canterbury engaged in less physically demanding activities than children from York or Newcastle. Within Canterbury, high-status and low-status children experienced similar biomechanical loading until around seven years of age. After this age low-status children performed activities that resulted in more habitual loading on their arm bones than the high-status children. This inferred change in physical activity is consistent with historical textual evidence that describes children entering the work force at this age

Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. Results: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders

Interglacial History of a Palaeo-lake and Regional Environment: A Multi-proxy Study of a Permafrost Deposit from Bolshoy Lyakhovsky Island, Arctic Siberia

Chironomid, pollen, and rhizopod records from a permafrost sequence at the Bolshoy Lyakhovsky Island (New Siberian Archipelago) document the evolution of a thermokarst palaeo-lake and environmental conditions in the region during the Last Interglacial (MIS 5e, ca. 130120 ka). Open Poaceae and Artemisia associations dominated vegetation at the beginning of the interglacial period, ca. 130 ka. Rare shrub thickets (Salix, Betula nana, Alnus fruticosa) grew in more protected and wetter places as well. Saalian ice wedges started to melt during this time, resulting in the formation of an initial thermokarst water body. The high percentage of semi-aquatic chironomids suggests that a peatland-pool palaeo-biotope existed at the site, when initial water body started to form. A distinct decrease in semi-aquatic chironomid taxa and an increase in lacustrine ones point to a gradual pooling of water in basin, which could in turn create thaw a permanent pond during the subsequent period. The highest relative abundance of Chironomus and Procladius reflects an existence of unfrozen water remaining under the ice throughout the ice-covered period during the later stage of palaeo-lake development. Chironomid record points to three successive stages during the water body evolution: (1) a peatland pool; (2) a pond (i.e., less deep than the maximum ice-cover thickness); and (3) a shallow lake (i.e., more deep than the maximum ice-cover thickness). The evolutionary trend of palaeo-lake points to intensive thermokarst processes occurring in the region during the Last Interglacial. Shrub tundra communities with Alnus fruticosa, Betula nana dominated the vegetation during the interglacial optimum that is evidenced by pollen record. The climate was relatively moist and warm. The results of this study suggest that quantitative chironomid-based temperature reconstructions from the Arctic thermokarst ponds/lakes may be problematic owing to other key environmental factors, such as prolonged periods of winter anoxia and local hydrological/geomorphological processes, controlling the chironomid assemblage