Differential effects of ERK and p38 signaling in BMP-2 stimulated hypertrophy of cultured chick sternal chondrocytes

Background During endochondral bone formation, the hypertrophy of chondrocytes is accompanied by selective expression of several genes including type X collagen and alkaline phosphatase. This expression is stimulated by inducers including BMPs and ascorbate. A 316 base pair region of the type X collagen (Col X) promoter has been previously characterized as the site required for BMP regulation. The intent of this study was to examine the role of Mitogen Activated Protein (MAP) and related kinase pathways in the regulation of Col X transcription and alkaline phosphatase activity in pre-hypertrophic chick chondrocytes. Results Using a luciferase reporter regulated by the BMP-responsive region of the type X collagen promoter, we show that promoter activity is increased by inhibition of extra-cellular signal regulated kinases 1 or 2 (ERK1/2). In contrast the ability of BMP-2 to induce alkaline phosphatase activity is little affected by ERK1/2 inhibition. The previously demonstrated stimulatory affect of p38 on Col X was shown to act specifically at the BMP responsive region of the promoter. The inhibitory effect of the ERK1/2 pathway and stimulatory effect of the p38 pathway on the Col X promoter were confirmed by the use of mutant kinases. Inhibition of upstream kinases: protein kinase C (PKC) and phosphatidylinositol 3-(PI3) kinase pathways increased basal Col X activity but had no effect on the BMP-2 induced increase. In contrast, ascorbate had no effect on the BMP-2 responsive region of the Col X promoter nor did it alter the increase in promoter activity induced by ERK1/2 inhibition. The previously shown increase in alkaline phosphatase activity induced by ascorbate was not affected by any kinase inhibitors examined. However some reduction in the alkaline phosphatase activity induced by the combination of BMP-2 and ascorbate was observed with ERK1/2 inhibition. Conclusion Our results demonstrate that ERK1/2 plays a negative role while p38 plays a positive role in the BMP-2 activated transcription of type X collagen. This regulation occurs specifically at the BMP-2 responsive promoter region of Col X. Ascorbate does not modulate Col X at this region indicating that BMP-2 and ascorbate exert their action on chondrocyte hypertrophy via different transcriptional pathways. MAP kinases seem to have only a modest effect on alkaline phosphatase when activity is induced by the combination of both BMP-2 and ascorbate

Second random-phase approximation with the Gogny force. First applications

We present the first applications of the second random-phase-approximation model with the finite-range Gogny interaction. We discuss the advantages of using such an interaction in this type of calculations where 2 particle-2 hole configurations are included. The results found in the present work confirm the well known general features of the second random-phase approximation spectra: we find a large shift, several MeV, of the response centroids to lower energies with respect to the corresponding random-phase-approximation values. As known, these results indicate that the effects of the 1 particle-1 hole/2 particle-2 hole and 2 particle-2 hole/2 particle-2 hole couplings are important. It has been found that the changes of the strength distributions with respect to the standard random-phase-approximation results are particularly large in the present case. This important effect is due to some large neutron-proton matrix elements of the interaction and indicates that these matrix elements (which do not contribute in the mean-field calculations employed in the conventional fit procedures of the force parameters) should be carefully constrained to perform calculation

Spatial energy spectrum of primordial magnetic fields

Here, we analyze the primordial magnetic field transition between a radiative and a matter-dominated universe. The gravitational structure formation affects its evolution and energy spectrum. The structure excitation can trigger magnetic field amplification and the steepening of its energy density spectrum.Comment: 8 pages, 2 figures, accepted for A&

Surgical management of ruptured small cerebral aneurysm: Outcome and surgical notes

Management of small aneurysms often poses a therapeutic dilemma and surgical treatment or coiling can be considered as therapeutic choices. In the present study, we reviewed our series of ruptured small cerebral aneurysm treated surgically

Housing system and welfare of buffalo (Bubalus bubalis) cows

Twenty-eight buffalo cows were used to evaluate the effect of housing system on a range of behavioural and physiological variables. Fourteen cows were group-housed in a loose open-sided barn with a concrete floor and 10 m2 per head as space allowance (group IS). Fourteen others were group-housed in a similar barn but they could also benefit from an outdoor yard with 500 m2 per head as space allowance, free access to potholes for wallowing and spontaneous vegetation (group TS). Animals were subjected to six sessions of instantaneous scan sampling at 10-day intervals. Behavioural variables were expressed as proportions of subjects observed in each category of posture and activity. Phytohaemagglutinin (PHA) was used to perform a skin test based on non-specific delayed type hypersensitivity, whereas 20 mg of ovalbumin were injected subcutaneously to evaluate humoral immune response. Blood samples for evaluation of cortisol concentration were collected immediately prior to exogenous porcine ACTH injection and 1, 2 and 4 h after. The metabolic status of the animals and milk production were also monitored. The proportion of idling animals was higher in group IS than in group TS (P< 0·001). More IS buffalo cows were observed eating at the manger than TS animals (P< 0·001). A higher proportion of TS animals were observed in the sun (P< 0·001). Grazing and bathing activities were recorded only for TS animals. Our findings suggest that buffalo cows kept in intensive conditions and having no access to ample yards and potholes may extend their periods of idling with negative effects on the state of welfare. Immune responses, metabolite concentrations and milk production were not affected by treatment, whereas cortisol levels were higher in IS animals (P< 0·05). The provision of a housing system similar to natural conditions was able to improve the welfare of buffalo cows as indicated by the expression of some species-specific natural behaviours. Such conditions were also associated with lower adrenal cortex response to ACTH injection, possibly as a consequence of the higher degree of initiative allowed to TS cows

Poteri e funzioni dello Stato: una voce per un dizionario di storia costituzionale

Il lavoro si propone di studiare le nozioni di potere e di funzione dello Stato, mediante una ricostruzione storico dommatica che parte dal pensiero politico di Locke e di Montesquieu per giungere sino alle sfide del costituzionalismo del Novecento. Esso accoglie, in particolare, una concezione oggettiva di funzione ed una concezione soggettiva di potere, ricostruendo poi, in chiave critica, i caratteri della teoria politica e giuridica della separazione dei poteri, per verificarne la perdurante validità in funzione di tutela delle libertà fondamentali dei cittadini

Temperature and finite-size effects in collective modes of superfluid Fermi gases

We study the effects of superfluidity on the monopole and quadrupole collective excitations of a dilute ultra-cold Fermi gas with an attractive interatomic interaction. The system is treated fully microscopically within the Bogoliubov-de Gennes and quasiparticle random-phase approximation methods. The dependence on the temperature and on the trap frequency is analyzed and systematic comparisons with the corresponding hydrodynamic predictions are presented in order to study the limits of validity of the semiclassical approach.Comment: 9 pages, 4 figure

On mixing angles and magnetic moment of heavy tau neutrino

If the magnetic moment of unstable tau neutrinos with the mass of $O$(MeV) is in the region of $10^{-8}\mu_{B} \lesssim \mu_{\nu_{\tau}} \lesssim 10^{-6}\mu_{B}$, it is compatible with the present experimental and cosmological bounds. It is pointed out here, that if the tau neutrino has such a large magnetic moment and can oscillate into a neutrino of another flavour the results from $\nu e$ scattering experiment at LAMPF constrain the tau neutrino mixing angles to $sin^{2}2\theta_{e \tau} \lesssim 2\times 10^{-6} - 2\times 10^{-2}$ and $sin^{2}2\theta_{\mu\tau} \lesssim 10^{-6} - 10^{-2}$ depending on the magnetic moment value in the allowed region.Comment: 5 pages, LaTe

Second--order equation of state with the Skyrme interaction. Cutoff and dimensional regularization with the inclusion of rearrangement terms

We evaluate the second--order (beyond--mean--field) contribution to the equation of state of nuclear matter with the effective Skyrme force and use cutoff and dimensional regularizations to treat the ultraviolet divergence produced by the zero--range character of this interaction. An adjustment of the force parameters is then performed in both cases to remove any double counting generated by the explicit computation of beyond--mean--field corrections with the Skyrme force. In addition, we include at second order the rearrangement terms associated to the density--dependent part of the Skyrme force and discuss their effect. Sets of parameters are proposed to define new effective forces which are specially designed for second--order calculations in nuclear matter.Comment: 29 figures, 9 table