Probable multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry 75: 924–925

Abstract: Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society Key words: Parkinson's disease; genetics; LRRK2; mutation Parkinson's disease (PD) is the second most common neurodegenerative disorder. Clinical features of PD include resting tremor, rigidity, bradykinesia, and postural instability. Although quite variable, the average age of onset is 60 years. In addition, there is a slight preponderance of affected men. Pathologically, PD is characterized by the presence of Lewy bodies and progressive degeneration of neurons in the substantia nigra, pars compacta, and other brain regions. In our ongoing effort to identify additional PD susceptibility genes, we have recruited a large cohort of PD families. The control sample was collected through three sources and provided appropriate written informed consent. One sample of controls (n ϭ 52) was ascertained in Indiana, and all control subjects were examined by a single Parkinson Study Group movement disorder specialist. These control subjects completed the identical clinical evaluation as the PD sample. Individuals were considered controls if they met the following criteria: did not have a diagnosis or symptoms of PD, Alzheimer's disease (AD), stroke, or other neurological disorder; no tremor; no other first-degree family members reported to be diagnosed with PD; and no history of polio. The average age at examination of these first control subjects was 68.3 years, with a range of 55 to 82 years. All individuals were non-Hispanic Caucasians. A second control sample (n ϭ 40) was obtained from the National Cell Repository for Alzheimer's Disease. The subjects were recruited as part of an ongoing genetic initiative to make available to the research community a sample of rigorously evaluated individuals without any evidence of neurological disease. All control subjects were evaluated, and there was no evidence for either PD or dementia. The average age at examination of the second control cohort was 76.9 years, with a range of 58 to 91 years. As was the case with the first control set, all subjects from the second control set were non-Hispanic Caucasians. DNA was prepared from peripheral blood samples collected from the PD families and control subjects. The third control sample (n ϭ 276) is composed of three neurologically normal Caucasian control panels (NDPT002, NDPT006, NDPT009) obtained from the NINDS Human Genetics Resource Center at the Coriell Institute Coriell Cell Repositories (Camden, NJ). This third control sample contains 132 males and 144 females. The average age at examination of the subjects was 69.7 years, with a range of 55 to 88 years. In total, 368 neurologically normal control samples were evaluated. The guanine to adenine substitution at nucleotide 4541 of the LRRK2 cDNA that results in the R1514Q Lrrk2 (dardarin) protein variant was screened for using a newly developed TaqMan allelic-discrimination assay (Applied Biosystems). The assay was performed with 30 ng of genomic DNA from each PD subject and control individual using conditions recommended by the manufacturer and an Applied Biosystems 7300 Real Time PCR System. Of 954 affected individuals from 12 different families, 16 (1.8%) were shown to be heterozygous carriers of the R1514Q variant. In addition, 5 (1.4%) of 368 control subjects were also found to be heterozygous for the same variant similar to the frequency observed by Zimprich and associates. Discordance for the mutation among affected individuals was observed in 10 of the 13 families in which the variant was segregating. Of the 28 affected individuals in these 12 families for whom DNA was available for study, 12 of them do not carry the R1514Q variant. This finding suggests that the R1514Q variant is not segregating with PD in these families. No statistically significant difference between the R1514Q carrier group (16) and the noncarrier group (938) was detected in our analyses of numerous parameters, including age of disease onset (61.75 years in R1514Q carriers vs. 60.9 years in noncarriers), disease duration (7.18 years carriers vs. 9.53 years noncarriers), Mini-Mental State Examination score (25.62 carriers vs. 26.48 noncarriers), Blessed Functional Activity Scale (3.66 carriers vs. 4.41 noncarriers), Hoehn & Yahr (2.2 carriers vs. 2.48 noncarriers), and ethnicity. Taken together, these data suggest that the R1514Q variant is likely a nonpathogenic variant in Lrrk2 that does not contribute to the development of Parkinson disease, confirming the report of Zimprich and coworkers

Lattice calculation of 1−+1^{-+} hybrid mesons with improved Kogut-Susskind fermions

We report on a lattice determination of the mass of the exotic $1^{-+}$ hybrid meson using an improved Kogut-Susskind action. Results from both quenched and dynamical quark simulations are presented. We also compare with earlier results using Wilson quarks at heavier quark masses. The results on lattices with three flavors of dynamical quarks show effects of sea quarks on the hybrid propagators which probably result from coupling to two meson states. We extrapolate the quenched results to the physical light quark mass to allow comparison with experimental candidates for the $1^{-+}$ hybrid meson. The lattice result remains somewhat heavier than the experimental result, although it may be consistent with the $\pi_1(1600)$.Comment: 24 pages, 12 figures. Replaced to match published versio

Is the Unitarity of the quark-mixing-CKM-matrix violated in neutron β\beta-decay?

We report on a new measurement of neutron $\beta$-decay asymmetry. From the result \linebreak $A_0$ = -0.1189(7), we derive the ratio of the axial vector to the vector coupling constant $\lambda$ = ${\it g_A/g_V}$ = -1.2739(19). When included in the world average for the neutron lifetime $\tau$ = 885.7(7)s, this gives the first element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix $V_{ud}$. With this value and the Particle Data Group values for $V_{us}$ and $V_{ub}$, we find a deviation from the unitarity condition for the first row of the CKM matrix of $\Delta$ = 0.0083(28), which is 3.0 times the stated error

Alpha scattering and capture reactions in the A = 7 system at low energies

Differential cross sections for $^3$He-$\alpha$ scattering were measured in the energy range up to 3 MeV. These data together with other available experimental results for $^3$He $+ \alpha$ and $^3$H $+ \alpha$ scattering were analyzed in the framework of the optical model using double-folded potentials. The optical potentials obtained were used to calculate the astrophysical S-factors of the capture reactions $^3$He$(\alpha,\gamma)^7$Be and $^3$H$(\alpha,\gamma)^7$Li, and the branching ratios for the transitions into the two final $^7$Be and $^7$Li bound states, respectively. For $^3$He$(\alpha,\gamma)^7$Be excellent agreement between calculated and experimental data is obtained. For $^3$H$(\alpha,\gamma)^7$Li a $S(0)$ value has been found which is a factor of about 1.5 larger than the adopted value. For both capture reactions a similar branching ratio of $R = \sigma(\gamma_1)/\sigma(\gamma_0) \approx 0.43$ has been obtained.Comment: submitted to Phys.Rev.C, 34 pages, figures available from one of the authors, LaTeX with RevTeX, IK-TUW-Preprint 930540

alpha-nucleus potentials for the neutron-deficient p nuclei

alpha-nucleus potentials are one important ingredient for the understanding of the nucleosynthesis of heavy neutron-deficient p nuclei in the astrophysical gamma-process where these p nuclei are produced by a series of (gamma,n), (gamma,p), and (gamma,alpha) reactions. I present an improved alpha-nucleus potential at the astrophysically relevant sub-Coulomb energies which is derived from the analysis of alpha decay data and from a previously established systematic behavior of double-folding potentials.Comment: 6 pages, 3 figures, accepted for publication in Phys. Rev.

Enhancing the top signal at Tevatron using Neural Nets

We show that Neural Nets can be useful for top analysis at Tevatron. The main features of $t\bar t$ and background events on a mixed sample are projected in a single output, which controls the efficiency and purity of the $t\bar t$ signal.Comment: 11 pages, 6 figures (not included and available from the authors), Latex, UB-ECM-PF 94/1