Caenorhabditis elegans glp-4 encodes a valyl aminoacyl tRNA synthetase

Germline stem cell proliferation is necessary to populate the germline with sufficient numbers of cells for gametogenesis and for signaling the soma to control organismal properties such as aging. The Caenorhabditis elegans gene glp-4 was identified by the temperature-sensitive allele bn2 where mutants raised at the restrictive temperature produce adults that are essentially germ cell deficient, containing only a small number of stem cells arrested in the mitotic cycle but otherwise have a morphologically normal soma. We determined that glp-4 encodes a valyl aminoacyl transfer RNA synthetase (VARS-2) and that the probable null phenotype is early larval lethality. Phenotypic analysis indicates glp-4(bn2ts) is partial loss of function in the soma. Structural modeling suggests that bn2 Gly296Asp results in partial loss of function by a novel mechanism: aspartate 296 in the editing pocket induces inappropriate deacylation of correctly charged Val-tRNA(val). Intragenic suppressor mutations are predicted to displace aspartate 296 so that it is less able to catalyze inappropriate deacylation. Thus glp-4(bn2ts) likely causes reduced protein translation due to decreased levels of Val-tRNA(val). The germline, as a reproductive preservation mechanism during unfavorable conditions, signals the soma for organismal aging, stress and pathogen resistance. glp-4(bn2ts) mutants are widely used to generate germline deficient mutants for organismal studies, under the assumption that the soma is unaffected. As reduced translation has also been demonstrated to alter organismal properties, it is unclear whether changes in aging, stress resistance, etc. observed in glp-4(bn2ts) mutants are the result of germline deficiency or reduced translation

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Foot-and-mouth disease virus (FMDV) causes economically-damaging infections of cloven-hooved animals, with outbreaks resulting in large financial losses to the agricultural industry. Due to the highly contagious nature of FMDV, research with infectious virus is restricted to a limited number of key facilities worldwide. FMDV subgenomic replicons are therefore important tools for the study of viral translation and genome replication. The type III phosphatidylinositol-4-kinases (PI4K) are a family of enzymes that play a key role in the production of replication complexes (viral factories) of a number of positive-sense RNA viruses and represents a potential target for novel pan-viral therapeutics. Here, we have investigated whether type III PI4Ks also play a role in the FMDV lifecycle, using a combination of FMDV subgenomic replicons and bicistronic IRES-containing reporter plasmids. We have demonstrated that replication of the FMDV replicon was unaffected by inhibitors of either PI4KIIIα or PI4KIIIβ. However, PIK93, an inhibitor previously demonstrated to target PI4KIIIβ, did inhibit IRES-mediated protein translation. Consistent with this, cells transfected with FMDV replicons did not exhibit elevated levels of PI4P lipids. These results are therefore supportive of the hypothesis that FMDV genome replication does not require type III PI4K activity and does not activate these kinases

SU(3)_flavor analysis of two-body weak decays of charmed baryons

We study two-body weak decays of charmed baryons \Lambda_c and \Xi_c into an octet or decuplet baryon and a pseudoscalar meson employing the SU(3) flavor symmetry. Using certain measured Cabibbo-favored modes, we fix the reduced amplitudes and predict the branching ratios of various decays of charmed baryons in the Cabibbo-enhanced, -suppressed and -doubly suppressed modes.Comment: 25 pages, No figure, Phys. Rev. D (to appear

Nonet Symmetry and Two-Body Decays of Charmed Mesons

The decay of charmed mesons into pseudoscalar (P) and vector (V) mesons is studied in the context of nonet symmetry. We have found that it is badly broken in the PP channels and in the P sector of the PV channels as expected from the non-ideal mixing of the \eta and the \eta'. In the VV channels, it is also found that nonet symmetry does not describe the data well. We have found that this discrepancy cannot be attributed entirely to SU(3) breaking at the usual level of 20--30%. At least one, or both, of nonet and SU(3) symmetry must be very badly broken. The possibility of resolving the problem in the future is also discussed.Comment: 9 pages, UTAPHY-HEP-

Replication Study of Candidate Genes Associated With Type 2 Diabetes Based On Genome-Wide Screening

OBJECTIVE—The present study was conducted to confirm possible associations between candidate genes from genome-wide association studies and type 2 diabetes in Japanese diabetic patients and a community-based general population. A total of 11 previously reported single-nucleotide polymorphisms (SNPs) from the TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2A/B, SLC30A8, and KCNJ11 genes were analyzed

Precise study of the resonance at Q0=(1,0,0) in URu2Si2

New inelastic neutron scattering experiments have been performed on URu2Si2 with special focus on the response at Q0=(1,0,0), which is a clear signature of the hidden order (HO) phase of the compound. With polarized inelastic neutron experiments, it is clearly shown that below the HO temperature (T0 = 17.8 K) a collective excitation (the magnetic resonance at E0 \approx 1.7 meV) as well as a magnetic continuum co-exist. Careful measurements of the temperature dependence of the resonance lead to the observation that its position shifts abruptly in temperature with an activation law governed by the partial gap opening and that its integrated intensity has a BCS-type temperature dependence. Discussion with respect to recent theoretical development is made

Magnetic Exciton Mediated Superconductivity in the Hidden-Order Phase of URu2Si2

We propose the magnetic exciton mediated superconductivity occurring in the enigmatic hidden-order phase of URu2Si2. The characteristic of the massive collective excitation observed only in the hidden-order phase is well reproduced by the antiferro hexadecapole ordering model as the trace of the dispersive crystalline-electric-field excitation. The disappearance of the superconductivity in the high-pressure antiferro magnetic phase can naturally be understood by the sudden suppression of the magnetic-exciton intensity. The analysis of the momentum dependence of the magnetic-exciton mode leads to the exotic chiral d-wave singlet pairing in the Eg symmetry. The Ising-like magnetic-field response of the mode yields the strong anisotropy observed in the upper critical field even for the rather isotropic 3-dimensional Fermi surfaces of this compound.Comment: 5 pages, 4 figure

Quasiparticle Inelastic Lifetime from Paramagnons in Disordered Superconductors

The paramagnon contribution to the quasiparticle inelastic scattering rate in disordered superconductors is presented. Using Anderson's exact eigenstate formalism, it is shown that the scattering rate is Stoner enhanced and is further enhanced by the disorder relative to the clean case in a manner similar to the disorder enhancement of the long-range Coulomb contribution. The results are discussed in connection with the possibility of conventional or unconventional superconductivity in the borocarbides. The results are compared to recent tunneling experiments on LuNi$_{2}$B$_{2}$C.Comment: 5 pages, no figure

The K2K SciBar Detector

A new near detector, SciBar, for the K2K long-baseline neutrino oscillation expe riment was installed to improve the measurement of neutrino energy spectrum and to study neutrino interactions in the energy region around 1 GeV. SciBar is a 'fully active' tracking detector with fine segmentation consisting of plastic scintillator bars. The detector was constructed in summer 2003 and is taking data since October 2003. The basic design and initial performance is presented.Comment: 7 pages, 4figures, Contributed to Proceedings of the 10th Vienna Conference on Instrumentation, Vienna, February 16-21, 200

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al