Modern meson--exchange potential and superfluid neutron star crust matter

In this work we study properties of neutron star crusts, where matter is expected to consist of nuclei surrounded by superfluid neutrons and a homogeneous background of relativistic electrons. The nuclei are disposed in a Coulomb lattice, and it is believed that the structure of the lattice influences considerably the specific heat of the neutronic matter inside the crust of a neutron star. Using a modern meson--exchange potential in the framework of a local--density approximation we calculate the neutronic specific heat accounting for various shapes of the Coulomb lattice, from spherical to non--spherical nuclear shapes. We find that a realistic nucleon--nucleon potential leads to a significant increase in the neutronic specific heat with respect to that obtained assuming a uniform neutron distribution. The increase is largest for the non--spherical phase of the crust. These results may have consequences for the thermal history of young neutron stars.Comment: Revtex, 5 pages, 4 figures included as uuencoded p

Microscopic structure of a vortex line in superfluid neutron star matter

The microscopic structure of an isolated vortex line in superfluid neutron star matter is studied by solving the Bogoliubov-de Gennes equations. Our calculation, which is the starting point for a microscopic calculation of pinning forces in neutron stars, shows that the size of the vortex core varies differently with density, and is in general smaller than assumed in some earlier calculations of vortex pinning in neutron star crusts. The implications of this result are discussedComment: 5 pages, 2 figure

Okadaic acid-Parthenolide combination at subtoxic doses induces potent synergistic apoptotic effects in human retinoblastoma Y79 cells by upregulating PTEN.

Retinoblastoma is the most common intraocular malignancy afflicting children. The incidence is higher in developing countries, where treatment is limited and long-term survival rates are low. Vincristine, etoposide, and carboplatin -the agents commonly used in the treatment of retinoblastoma- determine side effects causing significant morbidity to pediatric patients and significantly limiting dosing. Thus, identifying new drugs and molecular targets to facilitate the development of novel therapeutics, and finding natural drug combinations to kill cancer cells by synergistically acting at subtoxic doses, may be a good goal. Here, we investigated the effects of two natural compounds, okadaic acid (OKA) and parthenolide (PN), in human retinoblastoma Y79 cells. We showed that OKA/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by decrease in p-Akt, increase in the stabilized p53 forms and potent decrease in pS166\u2013Mdm2. We also showed the key involvement of PTEN which, after OKA/PN treatment, potently increased before p53, suggesting that p53 activation was under PTEN action. PTEN-knockdown increased p-Akt/ pS166Mdm2 over basal levels and significantly lowered p53, while OKA/PN treatment failed both to lower p-Akt and pS166\u2013Mdm2 and to increase p53 below/over their basal levels respectively. OKA/PN treatment potently increased ROS levels while decreased those of GSH. Reducing cellular GSH by butathionine-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKA/PN. The effects of OKA/PN treatment on both GSH content and cell viability were less pronounced in PTEN silenced cells than in control cells. Our study reports for the first time both a synergistic apoptotic action between OKA and PN and the involvement of PTEN as key player in the apoptotic mechanism in human retinoblastoma Y79 cells. The results provide strong suggestion for combined inhibition of the PTEN/Akt/Mdm2/p53 pathway

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HASH(0x563d43e27db0)HASH(0x563d44003f78

Variable maternal nutrition and growth hormone treatment in the second quarter of pregnancy in pigs alter semitendinosus muscle in adolescent progeny

Maternal nutrition and growth hormone (GH) treatment during early- to mid-pregnancy can each alter the subsequent growth and differentiation of muscle in progeny. We have investigated the effects of varying maternal nutrition and maternal treatment with porcine (p) GH during the second quarter of pregnancy in gilts on semitendinosus muscle cross-sectional area and fibre composition of progeny, and relationships between maternal and progeny measures and progeny muscularity. Fifty-three Large White×Landrace gilts, pregnant to Large White×Duroc boars, were fed either 2·2 kg (about 35 % ad libitum intake) or 3·0 kg commercial ration (13·5 MJ digestible energy, 150 g crude protein (N×6·25)/kg DM)/d and injected with 0, 4 or 8 mg pGH/d from day 25 to 50 of pregnancy, then all were fed 2·2 kg/d for the remainder of pregnancy. The higher maternal feed allowance from day 25 to 50 of pregnancy increased the densities of total and secondary fibres and the secondary:primary fibre ratio in semitendinosus muscles of their female progeny at 61 d of age postnatally. The densities of secondary and total muscle fibres in semitendinosus muscles of progeny were predicted by maternal weight before treatment and maternal plasma insulin-like growth factor-II during treatment. Maternal pGH treatment from day 25 to day 50 of pregnancy did not alter fibre densities, but increased the cross-sectional area of the semitendinosus muscle; this may be partially explained by increased maternal plasma glucose. Thus, maternal nutrition and pGH treatment during the second quarter of pregnancy in pigs independently alter muscle characteristics in progeny.Kathryn L. Gatford, Jason E. Ekert, Karina Blackmore, Miles J. De Blasio, Jodie M. Boyce, Julie A. Owens, Roger G. Campbell and Phillip C. Owen

In human retinoblastoma Y79 cells okadaic acid\u2013parthenolide co-treatment induces synergistic apoptotic effects, with PTEN as a key player.

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. here, we investigated the effects of two natural compounds okadaic acid (OKa) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKa/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-akt levels, increasing in the stabilized forms of p53 and potent decrease in ps166-Mdm2. We also showed the key involvement of PTeN which, after OKa/PN treatment, potently increased before p53, thus suggesting that p53 activation was under PTeN action. Moreover, after PTEN-knockdown p-akt/ ps166Mdm2 increased over basal levels and p53 significantly lowered, while OKa/PN treatment failed both to lower p-akt and ps166-Mdm2 and to increase p53 below/over their basal levels respectively. OKa/PN treatment potently increased ROs levels whereas decreased those of Gsh. Reducing cellular Gsh by l-butathionine-[s,R]-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKa/ PN. Furthermore, the effects of OKa/PN treatment on both Gsh content and cell viability were less pronounced in PTeN silenced cells than in control cells. The results provide strong suggestion for combining a treatment approach that targets the PTeN/akt/Mdm2/p53 pathway

Semiclassical Approximation to Neutron Star Superfluidity Corrected for Proximity Effects

The inner crust of a neutron star is a superfluid and inhomogeneous system, consisting of a lattice of nuclei immersed in a sea of neutrons. We perform a quantum calculation of the associated pairing gap and compare it to the results one obtains in the Local Density Approximation (LDA). It is found that the LDA overestimates the spatial dependence of the gap, and leads to a specific heat of the system which is too large at low temperatures, as compared with the quantal result. This is caused by the neglect of proximity effects and the delocalized character of the single-particle wavefunctions close to the Fermi energy. It is possible to introduce an alternative, simple semiclassical approximation of the pairing gap which leads to a specific heat that is in good agreement with the quantum calculation.Comment: RevteX, 8 Postscript Figure

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells.

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involvement in promoting proliferation, invasiveness, resistance to apoptosis and stemness. By RT-PCR, methylation-specific PCR, fluorescent in situ hybridization, DNA sequence, western blot and immunofluorescence analyses, we have shown that-in comparison with parental MG63 cells where TP53 gene is hypermethylated, rearranged and in single copy-in 3AB-OS cells, TP53 is unmethylated, rearranged and in multiple copies, and mutp53 (p53-R248W/P72R) is post-translationally modified and with nuclear localization. p53-R248W/P72R-knockdown by short-interfering RNA reduced the growth and replication rate of 3AB-OS cells, markedly increasing cell cycle inhibitor levels and sensitized 3AB-OS cells to TRAIL-induced apoptosis by DR5 up-regulation; moreover, it strongly decreased the levels of stemness and invasiveness genes. We have also found that the ectopic expression of p53-R248W/P72R in MG63 cells promoted cancer stem-like features, as high proliferation rate, sphere formation, clonogenic growth, high migration and invasive ability; furthermore, it strongly increased the levels of stemness proteins. Overall, the findings suggest the involvement of p53-R248W/P72R at the origin of the aberrant characters of the 3AB-OS cells with the hypothesis that its GOF can be at the root of the dedifferentiation of MG63 cells into CSCs

Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques from 42 consecutive patients undergoing carotid endarterectomy were stained with hematoxylin-eosin and the lipid core, cholesterol clefts, hemorrhagic content, thickness of tunica media, and intima, including or not infiltration of cellular debris and cholesterol, were determined. The presence of ficolin-1, -2, and -3 and mannose-binding lectin (MBL), LP initiators, was assessed in the plaques by immunofluorescence and in plasma by ELISA. LP activation was assessed in plasma by functional in vitro assays. Patients presenting low stenosis (≤75%) had higher hemorrhagic content than those with high stenosis (>75%), indicating increased erosion. Increased hemorrhagic content and tunica media thickness, as well as decreased lipid core and infiltrated content were associated with vulnerable plaques and therefore used to establish a plaque vulnerability score that allowed to classify patients according to plaque vulnerability. Ficolins and MBL were found both in plaques’ necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1. We show that the LP initiators are present within the plaques and their circulating levels change in atherosclerotic patients. In particular, we show that decreased ficolin-2 levels are associated with rupture-prone vulnerable plaques, indicating its potential use as marker for cardiovascular risk assessment in atherosclerotic patients