Application of realistic effective interactions to the structure of the Zr isotopes

We calculate the low-lying spectra of the zirconium isotopes Z=40 with neutron numbers from N=52 to N=60 using the 1p1/20g9/2 proton and 2s1d0g7/20h11/2 neutron sub-shells to define the model space. Effective proton-proton, neutron--neutron and proton-neutron interactions have been derived using 88Sr as closed core and employing perturbative many-body techniques. The starting point is the nucleon-nucleon potential derived from modern meson exchange models. The comprehensive shell-model calculation performed in this work provides a qualitative reproduction of essential properties such as the sub-shell closures in 96Zr and 98Zr.Comment: To appear in Phys Rev C, june 2000, 8 figs, Revtex latex styl

New calculations of the PNC Matrix Element for the JπTJ^{\pi}T 0+1,0−1^{+}1,0^{-}1 doublet in 14^{14}N

A new calculation of the predominantly isoscalar PNC matrix element between the $J^{\pi}T$ $0^{+}1,0^{-}1$ (E$_{x} \approx$ 8.7 MeV) states in $^{14}$N has been carried out in a (0+1+2+3+4)$\hbar \omega$ model space with the Warburton-Brown interaction. The magnitude of the PNC matrix element of 0.22 to 0.34 eV obtained with the DDH PNC interaction is substantially suppressed compared with previous calculations in smaller model spaces but shows agreement with the preliminary Seattle experimental data. The calculated sign is opposite to that obtained experimentally, and the implications of this are discussed.Comment: REVTEX, 28 page

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2

Background: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson’s disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro. Methodology/Principal Findings: Here, we show that the rho guanine nucleotide exchange factor ARHGEF7 and the small GTPase CDC42 are interacting with LRRK2 in vitro and in vivo. GTPase activity of full-length LRRK2 increases in the presence of recombinant ARHGEF7. Interestingly, LRRK2 phosphorylates ARHGEF7 in vitro at previously unknown phosphorylation sites. We provide evidence that ARHGEF7 might act as a guanine nucleotide exchange factor for LRRK2 and that R1441C mutant LRRK2 with reduced GTP hydrolysis activity also shows reduced binding to ARHGEF7. Conclusions/Significance: Downstream effects of phosphorylation of ARHGEF7 through LRRK2 could be (i) a feedback control mechanism for LRRK2 activity as well as (ii) an impact of LRRK2 on actin cytoskeleton regulation. A newly identified familial mutation N1437S, localized within the GTPase domain of LRRK2, further underlines the importance of the GTPas

Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease

Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD

The LRRK2 G2385R variant is a partial loss-of-function mutation that affects synaptic vesicle trafficking through altered protein interactions.

Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson's disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed the functional features attributed to LRRK2 by its N- and C-terminal domains. We combined TIRF microscopy and synaptopHluorin assay to visualize synaptic vesicle trafficking. We found that N- and C-terminal domains have opposite impact on synaptic vesicle dynamics. Biochemical analysis demonstrated that different proteins are bound at the two extremities, namely \u3b23-Cav2.1 at N-terminus part and \u3b2-Actin and Synapsin I at C-terminus domain. A sequence variant (G2385R) harboured within the C-terminal WD40 domain increases the risk for PD. Complementary biochemical and imaging approaches revealed that the G2385R variant alters strength and quality of LRRK2 interactions and increases fusion of synaptic vesicles. Our data suggest that the G2385R variant behaves like a loss-of-function mutation that mimics activity-driven events. Impaired scaffolding capabilities of mutant LRRK2 resulting in perturbed vesicular trafficking may arise as a common pathophysiological denominator through which different LRRK2 pathological mutations cause diseas

Gamow-Teller Strength in the Region of 100^{100}Sn

New calculations are presented for Gamow-Teller beta decay of nuclei near $^{100}$Sn. Essentially all of the $^{100}$Sn Gamow-Teller decay strength is predicted to go to a single state at an excitation energy of 1.8 MeV in $^{100}$In. The first calculations are presented for the decays of neighboring odd-even and odd-odd nuclei which show, in contrast to $^{100}$Sn, surprisingly complex and broad Gamow-Teller strength distributions. The results are compared to existing experimental data and the resulting hindrance factors are discussed.Comment: 12 pages (latex) and 2 figures available on reques

Toward a Consistent Description of the PNC Experiments in A=18-21 Nuclei

The experimental PNC results in $^{18}$F, $^{19}$F, $^{21}$Ne and the current theoretical analysis show a discrepancy . If one interprets the small limit of the experimentally extracted PNC matrix element for $^{21}$Ne as a destructive interference between the isoscalar and the isovector contribution, then it is difficult to understand why the isovector contribution in $^{18}$F is so small while the isoscalar + isovector contribution in $^{19}$F is relatively large. In order to understand the origin of this discrepancy a comparison of the calculated PNC matrix elements was performed. It is shown that the $^{18}$F and $^{21}$Ne matrix elements contain important contributions from 3$\hbar \omega$ and 4$\hbar \omega$ configuration and that the (0+1)$\hbar \omega$ calculations give distorted results.Comment: REVTEX, 16 pages, 1 postscriptum figure uuencoded and appende

Doubly Constrained C-terminal of Roc (COR) Domain-Derived Peptides Inhibit Leucine-Rich Repeat Kinase 2 (LRRK2) Dimerization

Missense mutations along the leucine-rich repeat kinase 2 (LRRK2) protein are a major contributor to Parkinson's Disease (PD), the second most commonly occurring neurodegenerative disorder worldwide. We recently reported the development of allosteric constrained peptide inhibitors that target and downregulate LRRK2 activity through disruption of LRRK2 dimerization. In this study, we designed doubly constrained peptides with the objective of inhibiting C-terminal of Roc (COR)-COR mediated dimerization at the LRRK2 dimer interface. We show that the doubly constrained peptides are cell-permeant, bind wild-type and pathogenic LRRK2, inhibit LRRK2 dimerization and kinase activity, and inhibit LRRK2-mediated neuronal apoptosis, and in contrast to ATP-competitive LRRK2 kinase inhibitors, they do not induce the mislocalization of LRRK2 to skein-like structures in cells. This work highlights the significance of COR-mediated dimerization in LRRK2 activity while also highlighting the use of doubly constrained peptides to stabilize discrete secondary structural folds within a peptide sequence.</p

Shell Model Monte Carlo studies of neutron-rich nuclei in the 1s-0d-1p-0f shells

We demonstrate the feasibility of realistic Shell-Model Monte Carlo (SMMC) calculations spanning multiple major shells, using a realistic interaction whose bad saturation and shell properties have been corrected by a newly developed general prescription. Particular attention is paid to the approximate restoration of translational invariance. The model space consists of the full sd-pf shells. We include in the study some well-known T=0 nuclei and several unstable neutron-rich ones around N=20,28. The results indicate that SMMC can reproduce binding energies, B(E2) transitions, and other observables with an interaction that is practically parameter free. Some interesting insight is gained on the nature of deep correlations. The validity of previous studies is confirmed.Comment: 22 pages + 7 postscript figure

Microscopic theories of neutrino-^{12}C reactions

In view of the recent experiments on neutrino oscillations performed by the LSND and KARMEN collaborations as well as of future experiments, we present new theoretical results of the flux averaged $^{12}C(\nu_e,e^-)^{12}N$ and $^{12}C(\nu_{\mu},{\mu}^-)^{12}N$ cross sections. The approaches used are charge-exchange RPA, charge-exchange RPA among quasi-particles (QRPA) and the Shell Model. With a large-scale shell model calculation the exclusive cross sections are in nice agreement with the experimental values for both reactions. The inclusive cross section for $\nu_{\mu}$ coming from the decay-in-flight of $\pi^+$ is $15.2 \times 10^{-40} cm^2$ to be compared to the experimental value of $12.4 \pm 0.3 \pm 1.8 \times 10^{-40} cm^2$, while the one due to $\nu_{e}$ coming from the decay-at-rest of $\mu^+$ is $16.4 \times 10^{-42} cm^2$ which agrees within experimental error bars with the measured values. The shell model prediction for the decay-in-flight neutrino cross section is reduced compared to the RPA one. This is mainly due to the different kind of correlations taken into account in the calculation of the spin modes and partially due to the shell-model configuration basis which is not large enough, as we show using arguments based on sum-rules.Comment: 17 pages, latex, 5 figure