Exclusive K+K^+ production in proton-nucleus collisions

The exclusive $K^+$ meson production in a proton-nucleus collision, leading to two body final states, is investigated in a fully covariant two-nucleon model based on the effective Lagrangian picture. The explicit kaon production vertex is described via creation, propagation and decay into relevant channel of $N^*$(1650), $N^*$(1710) and $N^*$(1720) intermediate baryonic states in the initial collision of the projectile nucleon with one of its target counterparts which is modeled by the one-pion exchange process. The calculated cross sections show strong sensitivity to the medium effects on pion propagator and to the final hypernuclear state excited in the reaction.Comment: Two new figures, version accepted for publication by Phys. Rev.

Variational calculations of the Λ\Lambda-seperation energy of the Λ17_{\Lambda}^{17}O hypernucleus

Variational Monte Carlo calculations have been made for the $_{ \Lambda}^{17}$O hypernucleus using realistic two- and three-baryon interactions. A two pion exchange potential with spin- and space-exchange components is used for the $\Lambda$N potential. Three-body two-pion exchange and strongly repulsive dispersive $\Lambda$NN interactions are also included. The trial wave function is constructed from pair- and triplet-correlation operators acting on a single particle determinant. These operators consist of central, spin, isospin, tensor and three- baryon potential components. A cluster Monte Carlo method is developed for noncentral correlations and is used with up to four-baryon clusters in our calculations. The three-baryon $\Lambda$NN force is discussed.Comment: 24 pages, 2 figs available by fax., for publication in Phys. Rev.

A Realistic Description of Nucleon-Nucleon and Hyperon-Nucleon Interactions in the SU_6 Quark Model

We upgrade a SU_6 quark-model description for the nucleon-nucleon and hyperon-nucleon interactions by improving the effective meson-exchange potentials acting between quarks. For the scalar- and vector-meson exchanges, the momentum-dependent higher-order term is incorporated to reduce the attractive effect of the central interaction at higher energies. The single-particle potentials of the nucleon and Lambda, predicted by the G-matrix calculation, now have proper repulsive behavior in the momentum region q_1=5 - 20 fm^-1. A moderate contribution of the spin-orbit interaction from the scalar-meson exchange is also included. As to the vector mesons, a dominant contribution is the quadratic spin-orbit force generated from the rho-meson exchange. The nucleon-nucleon phase shifts at the non-relativistic energies up to T_lab=350 MeV are greatly improved especially for the 3E states. The low-energy observables of the nucleon-nucleon and the hyperon-nucleon interactions are also reexamined. The isospin symmetry breaking and the Coulomb effect are properly incorporated in the particle basis. The essential feature of the Lambda N - Sigma N coupling is qualitatively similar to that obtained from the previous models. The nuclear saturation properties and the single-particle potentials of the nucleon, Lambda and Sigma are reexamined through the G-matrix calculation. The single-particle potential of the Sigma hyperon is weakly repulsive in symmetric nuclear matter. The single-particle spin-orbit strength for the Lambda particle is very small, in comparison with that of the nucleons, due to the strong antisymmetric spin-orbit force generated from the Fermi-Breit interaction.Comment: Revtex v2.09, 69 pages with 25 figure

Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ

Wnt addiction of genetically defined cancers reversed by PORCN inhibition

Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers

Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of <it>CDH1 </it>germline mutations in gastric cancers coming from low- and high-risk areas.</p> <p>Methods</p> <p>English articles using MEDLINE access (from 1998 to 2011). Search terms included <it>CDH1</it>, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype.</p> <p>The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded.</p> <p>The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the <it>CDH1 </it>mutation frequency with gastric cancer incidence areas.</p> <p>Results</p> <p>A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (<it>p </it>< 0.001: overall identified mutations in low- vs. middle/high-risk areas).</p> <p>Conclusions</p> <p>E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of <it>CDH1 </it>germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the <it>CDH1 </it>genetic screening, geographic variability, alongside the family history should be considered.</p

Murine Cytomegalovirus Infection of Neural Stem Cells Alters Neurogenesis in the Developing Brain

Congenital cytomegalovirus (CMV) brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV) and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs) and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi) cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons

First observation of the hyper superheavy hydrogen 6{\Lambda}H

Three candidate events of the neutron-rich hypernucleus 6{\Lambda}H were uniquely identified in the FINUDA experiment at DA{\Phi}NE, Frascati, by observing {\pi}+ mesons from the (K-stop,{\pi}+) production reaction on 6Li targets, in coincidence with {\pi}-mesons from 6{\Lambda}H \rightarrow 6He+{\pi}- weak decay. Details of the experiment and the analysis of its data are reported, leading to an estimate of (2.9\pm2.0)\cdot10-6/K- stop for the 6{\Lambda}H production rate times the two-body {\pi}- weak decay branching ratio. The 6{\Lambda}H binding energy with respect to 5H + {\Lambda} was determined jointly from production and decay to be B{\Lambda} = (4.0 \pm 1.1) MeV, assuming that 5H is unbound with respect to 3H + 2n by 1.7 MeV. The binding energy determined from production is higher, in each one of the three events, than that determined from decay, with a difference of (0.98 \pm 0.74) MeV here assigned to the 0+g.s. \rightarrow 1+ excitation. The consequences of this assignment to {\Lambda} hypernuclear dynamics are briefly discussed.Comment: 20 pages, 8 figures, version matching published Nuclear Physics A manuscrip