The Striking Flower-in-Flower Phenotype of Arabidopsis thaliana Nossen (No-0) is Caused by a Novel LEAFY Allele

The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: Firstly, cauline leaves with axillary meristems are formed and internode elongation begins. Secondly, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a transposon insertion mutant in the Nossen accession with defects in floral development and growth. Most strikingly is the outgrowth of stems from the axillary bracts of the primary flower carrying secondary flowers. Therefore, we named this mutant flower-in-flower (fif). However, the transposon insertion in the annotated gene is not the cause for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY gene. The mutation, a G-to-A exchange in the second exon of LEAFY, creates a novel lfy allele and results in a cysteine-to-tyrosine exchange in the α1-helix of LEAFY’s DNA-binding domain. This exchange abolishes target DNA-binding, whereas subcellular localization and homomerization are not affected. To explain the strong fif phenotype against these molecular findings, several hypotheses are discussed

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

LRRK2 transport is regulated by its novel interacting partner Rab32

Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain 280 kDa protein that is linked to Parkinson's disease (PD). Mutations especially in the GTPase and kinase domains of LRRK2 are the most common causes of heritable PD and are also found in sporadic forms of PD. Although the cellular function of LRRK2 is largely unknown there is increasing evidence that these mutations cause cell death due to autophagic dysfunction and mitochondrial damage. Here, we demonstrate a novel mechanism of LRRK2 binding and transport, which involves the small GTPases Rab32 and Rab38. Rab32 and its closest homologue Rab38 are known to organize the trans-Golgi network and transport of key enzymes in melanogenesis, whereas their function in non-melanogenic cells is still not well understood. Cellular processes such as autophagy, mitochondrial dynamics, phagocytosis or inflammatory processes in the brain have previously been linked to Rab32. Here, we demonstrate that Rab32 and Rab38, but no other GTPase tested, directly interact with LRRK2. GFP-Trap analyses confirmed the interaction of Rab32 with the endogenous LRRK2. In yeast two-hybrid experiments we identified a predicted coiled-coil motif containing region within the aminoterminus of LRRK2 as the possible interacting domain. Fluorescence microscopy demonstrated a co-localization of Rab32 and LRRK2 at recycling endosomes and transport vesicles, while overexpression of a constitutively active mutant of Rab32 led to an increased co-localization with Rab7/9 positive perinuclear late endosomes/MVBs. Subcellular fractionation experiments supported the novel role of Rab32 in LRRK2 late endosomal transport and sorting in the cell. Thus, Rab32 may regulate the physiological functions of LRRK2

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

Signal Transduction Protein Array Analysis Links LRRK2 to Ste20 Kinases and PKC Zeta That Modulate Neuronal Plasticity

substrate phosphorylation..Ste20 kinases and PKC zeta contribute to neuronal Tau phosphorylation, neurite outgrowth and synaptic plasticity under physiological conditions. Our data suggest that these kinases may also be involved in synaptic dysfunction and neurite fragmentation in transgenic mice and in human PD patients carrying toxic gain-of-function LRRK2 mutations

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

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

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target