Assessment of an osteoblast-like cell line as a model for human primary osteoblasts using Raman spectroscopy

Raman spectroscopy is employed to determine the suitability of the U20S osteoblast-like cell line for use as a model for human primary osteoblasts, with emphasis on the ability of these cell types to replicate their tissue of origin. It was found that both cell types demonstrated early stage mineral deposition that followed significantly different growth patterns. Analysis of the growth pattern and spectral data from primary cells revealed increasing bone quality ratios and a high crystallinity, consistent with previous reports. Conversely the investigation of the U20S osteoblast-like cell line provided evidence of dense multilayered mineralised regions that corresponded more closely to native bone in terms of its crystallinity and bone quality ratios. This finding contradicts previous reports on U20S osteoblast-like cells which have consistently described them as non-osteoinductive when cultured in various conditions on a number of substrates. This work demonstrates the successful application of Raman spectroscopy combined with biological and multivariate analysis for the investigation of osteoblast-like U20S cells and human primary osteoblasts, specifically with focus on the osteoinductive ability of the osteoblast-like cell line and the comparative differences in relation to the primary osteoblasts

Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex.

The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain

Bone versus breast density

The common link with oestrogen levels suggests that bone mineral density and mammographic density might also be linked. One study found weak support for this, but another study failed to provide confirmation. Overall, the relationship is very weak, if it exists at all. Other factors such as weight-bearing exercise, which have opposing impacts on these variables, may have a more dominant effect

D'Alembert‐type solution of the Cauchy problem for the Boussinesq‐Klein‐Gordon equation

In this paper, we construct a weakly‐nonlinear d'Alembert‐type solution of the Cauchy problem for the Boussinesq‐Klein‐Gordon (BKG) equation. Similarly to our earlier work based on the use of spatial Fourier series, we consider the problem in the class of periodic functions on an interval of finite length (including the case of localized solutions on a large interval), and work with the nonlinear partial differential equation with variable coefficients describing the deviation from the oscillating mean value. Unlike our earlier paper, here we develop a novel multiple‐scales procedure involving fast characteristic variables and two slow time scales and averaging with respect to the spatial variable at a constant value of one or another characteristic variable, which allows us to construct an explicit and compact d'Alembert‐type solution of the nonlinear problem in terms of solutions of two Ostrovsky equations emerging at the leading order and describing the right‐ and left‐propagating waves. Validity of the constructed solution in the case when only the first initial condition for the BKG equation may have nonzero mean value follows from our earlier results, and is illustrated numerically for a number of instructive examples, both for periodic solutions on a finite interval, and localized solutions on a large interval. We also outline an extension of the procedure to the general case, when both initial conditions may have nonzero mean values. Importantly, in all cases, the initial conditions for the leading‐order Ostrovsky equations by construction have zero mean, while initial conditions for the BKG equation may have nonzero mean values

Mammographic density does not correlate with Ki-67 expression or cytomorphology in benign breast cells obtained by random periareolar fine needle aspiration from women at high risk for breast cancer

BACKGROUND:Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.METHODS:Included in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by ?2 test, and continuous variables were analyzed by nonparametric test and linear regression.RESULTS:Forty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P = 0.001) and younger age (=50 years versus >50 years; P = 0.001). Mammographic density was higher in premenopausal women (P = 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.CONCLUSION:Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials