Enhanced osteogenic differentiation in zoledronate-treated osteoporotic patients

Bisphosphonates are well known inhibitors of osteoclast activity and thus may be employed to influence osteoblast activity. The present study was designed to evaluate the in vivo effects of zoledronic acid (ZA) on the proliferation and osteoblastic commitment of mesenchymal stem cells (MSC) in osteoporotic patients. We studied 22 postmenopausal osteoporotic patients. Densitometric, biochemical, cellular and molecular data were collected before as well as after 6 and 12 months of ZA treatment. Peripheral blood MSC-like cells were quantified by colony-forming unit fibroblastic assay; their osteogenic differentiation potential was evaluated after 3 and 7 days of induction, respectively. Circulating MSCs showed significantly increased expression levels of osteoblastic marker genes such as Runt-related transcription factor 2 (RUNX2), and Osteonectin (SPARC) during the 12 months of monitoring time. Lumbar bone mineral density (BMD) variation and SPARC gene expression correlated positively. Bone turnover marker levels were significantly lowered after ZA treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase (bALP). Our findings suggest a discrete anabolic activity supported by osteogenic commitment of MSCs, consequent to ZA treatment. We confirm its anabolic effects in vivo on osteogenic precursors

STOCHASTIC DYNAMICS OF TWO PICOPHYTOPLANKTON POPULATIONS IN A REAL MARINE ECOSYSTEM

A stochastic reaction-diffusion-taxis model is analyzed to get the stationary distribution along water column of two species of picophytoplankton, that is picoeukaryotes and Prochlorococcus. The model is valid for weakly mixed waters, typical of the Mediterranean Sea. External random fluctuations are considered by adding a multiplicative Gaussian noise to the dynamical equation of the nutrient concentration. The statistical tests show that shape and magnitude of the theoretical concentration profile exhibit a good agreement with the experimental findings. Finally, we study the effects of seasonal variations on picophytoplankton groups, including an oscillating term in the auxiliary equation for the light intensity

Dynamics of Two Picophytoplankton Groups in Mediterranean Sea: Analysis of the Deep Chlorophyll Maximum by a Stochastic Advection-Reaction-Diffusion Model

A stochastic advection-reaction-diffusion model with terms of multiplicative white Gaussian noise, valid for weakly mixed waters, is studied to obtain the vertical stationary spatial distributions of two groups of picophytoplankton, i.e., picoeukaryotes and Prochlorococcus, which account about for 60% of total chlorophyll on average in Mediterranean Sea. By numerically solving the equations of the model, we analyze the one-dimensional spatio-temporal dynamics of the total picophytoplankton biomass and nutrient concentration along the water column at different depths. In particular, we integrate the equations over a time interval long enough, obtaining the steady spatial distributions for the cell concentrations of the two picophytoplankton groups. The results are converted into chlorophyll a and divinil chlorophyll a concentrations and compared with experimental data collected in two different sites of the Sicily Channel (southern Mediterranean Sea). The comparison shows that real distributions are well reproduced by theoretical profiles. Specifically, position, shape and magnitude of the theoretical deep chlorophyll maximum exhibit a good agreement with the experimental values

Mean Escape Time in a System with Stochastic Volatility

We study the mean escape time in a market model with stochastic volatility. The process followed by the volatility is the Cox Ingersoll and Ross process which is widely used to model stock price fluctuations. The market model can be considered as a generalization of the Heston model, where the geometric Brownian motion is replaced by a random walk in the presence of a cubic nonlinearity. We investigate the statistical properties of the escape time of the returns, from a given interval, as a function of the three parameters of the model. We find that the noise can have a stabilizing effect on the system, as long as the global noise is not too high with respect to the effective potential barrier experienced by a fictitious Brownian particle. We compare the probability density function of the return escape times of the model with those obtained from real market data. We find that they fit very well.Comment: 9 pages, 9 figures, to be published in Phys. Rev.

The role of noise on the steady state distributions of phytoplankton populations

The spatio-temporal behaviour of total chlorophyll concentration is investigated in the middle of the Tyrrhenian Sea by using a stochastic approach. The study is based on a reaction-diffusion-taxis model, which is used to analyse the dynamics of five phytoplankton groups, responsible for about 80% of the total chlorophyll a inside the euphotic zone of the water column. The analysis is performed by considering: (i) the intraspecific competition of the phytoplanktonic groups for limiting factors, i.e. light intensity and nutrient concentration, (ii) the seasonal changes of environmental variables, and (iii) the random fluctuations of the components of the velocity field and temperature. Specifically, we investigate the effects of external perturbations, both deterministic and random, on the dynamics of phytoplankton populations, by inserting a term of multiplicative noise into the differential equation of the nutrient dynamics. The theoretical results of the phytoplankton abundances obtained by the stochastic model are converted in chlorophyll a concentrations, and compared with the experimental findings. The statistical checks, based on the chi-square test, show that the vertical distributions of total chlorophyll concentration are in a good agreement with the experimental data. Finally, we observe that the high intensity of environmental noise strongly modifies the steady spatial distributions of two phytoplankton groups usually localized in deeper layers, causing algal blooms in surface water

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy

A UBVI and uvbyCaHbeta Analysis of the Intermediate-Age Open Cluster, NGC 5822

NGC 5822 is a richly populated, moderately nearby, intermediate-age open cluster covering an area larger than the full moon on the sky. A CCD survey of the cluster on the UBVI and uvbyCaHbeta systems shows that the cluster is superposed upon a heavily reddened field of background stars with E(B-V) > 0.35 mag, while the cluster has small and uniform reddening at E(b-y) = 0.075 +/- 0.008 mag or E(B-V) = 0.103 +/- 0.011 mag, based upon 48 and 61 probable A and F dwarf single-star members, respectively. The errors quoted include both internal photometric precision and external photometric uncertainties. The metallicity derived from 61 probable single F-star members is [Fe/H] = -0.058 +/- 0.027 (sem) from m_1 and 0.010 +/- 0.020 (sem) from hk, for a weighted average of [Fe/H] = -0.019 +/- 0.023, where the errors refer to the internal errors from the photometry alone. With reddening and metallicity fixed, the cluster age and apparent distance modulus are obtained through a comparison to appropriate isochrones in both VI and BV, producing 0.9 +/- 0.1 Gyr and 9.85 +/- 0.15, respectively. The giant branch remains dominated by two distinct clumps of stars, though the brighter clump seems a better match to the core-He-burning phase while the fainter clump straddles the first-ascent red giant branch. Four potential new clump members have been identified, equally split between the two groups. Reanalysis of the UBV two-color data extending well down the main sequence shows it to be optimally matched by reddening near E(B-V) = 0.10 rather than the older value of 0.15, leading to [Fe/H] between -0.16 and 0.00 from the ultraviolet excess of the unevolved dwarfs. The impact of the lower reddening and younger age of the cluster on previous analyses of the cluster is discussed.Comment: 20 figures and 5 tables (portions of data tables 3 and 5 only

Potential biogas production from agricultural by-products in Sicily. A case study of citrus pulp and olive pomace

Renewable energy sources represent a suitable alternative to conventional fossil fuels, due to the possible advantages in terms of environmental impact reduction. Anaerobic digestion of biomasses could be considered an environmental friendly way to treat and revalorise large amounts of by-products from farming industries because it ensures both pollution control and energy recovery. Therefore, the objective of this study was to define a methodology for evaluating the potential biogas production available from citrus pulp and olive pomace, which are suitable agricultural by-products for biogas production. In the first phase of the study, the spatial distribution of both olive and citrus-producing areas was analysed in Sicily, a geographical area of the Mediterranean basin highly representative of these types of cultivation. Then, a GIS-based model, which had been previously defined and utilised to evaluate the amount of citrus pulp and olive pomace production, was applied to this case study. Based on the results obtained for the different provinces of Sicily, the province of Catania was chosen as the study area of this work since it showed the highest production of both citrus pulp and olive pomace. Therefore, a further analysis regarded the quantification of olive pomace and citrus pulp at municipal level. The results of this analysis showed that the total amount of available citrus pulp and olive pomace corresponded theoretically to about 11,102,469 Nm3/year biogas. Finally, the methodology adopted in this study made it possible to identify suitable areas for the development of new biogas plants by considering both the spatial distribution of the olive and citrus growing areas and the locations of the existing processing industries