Radiation-induced Assembly of Rad51 and Rad52 Recombination Complex Requires ATM and c-Abl

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R

Inhibition of Striatal Soluble Guanylyl Cyclase-cGMP Signaling Reverses Basal Ganglia Dysfunction and Akinesia in Experimental Parkinsonism

There is clearly a necessity to identify novel non-dopaminergic mechanisms as new therapeutic targets for Parkinson's disease (PD). Among these, the soluble guanylyl cyclase (sGC)-cGMP signaling cascade is emerging as a promising candidate for second messenger-based therapies for the amelioration of PD symptoms. In the present study, we examined the utility of the selective sGC inhibitor 1H-[1], [2], [4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) for reversing basal ganglia dysfunction and akinesia in animal models of PD.The utility of the selective sGC inhibitor ODQ for reversing biochemical, electrophysiological, histochemical, and behavioral correlates of experimental PD was performed in 6-OHDA-lesioned rats and mice chronically treated with MPTP.We found that one systemic administration of ODQ is sufficient to reverse the characteristic elevations in striatal cGMP levels, striatal output neuron activity, and metabolic activity in the subthalamic nucleus observed in 6-OHDA-lesioned rats. The latter outcome was reproduced after intrastriatal infusion of ODQ. Systemic administration of ODQ was also effective in improving deficits in forelimb akinesia induced by 6-OHDA and MPTP.Pharmacological inhibition of the sGC-cGMP signaling pathway is a promising non-dopaminergic treatment strategy for restoring basal ganglia dysfunction and attenuating motor symptoms associated with PD

Sarcopenic Obesity: Prevalence and Association With Metabolic Syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA)

OBJECTIVE - We investigated the prevalence of sarcopenic obesity (SO) and its relationship with metabolic syndrome in a community-based elderly cohort in Korea. RESEARCH DESIGN AND METHODS - In this study, 287 men and 278 women aged 65 or older were recruited. Sarcopenia was defined as the appendicular skeletal muscle mass (ASM) divided by height squared (Ht(2)) (kg/m(2)) or by weight (Wt) (%) of = 100 cm(2). RESULTS - The prevalence of SO was 16.7% in men and 5.7% in women with sarcopenia defined by ASM/Ht(2); however, it was 35.1% in men and 48.1% in women by ASM/Wt. Using ASM/Wt, the homeostasis model assessment of insulin resistance of subjects with SO was higher and they were at higher risk for metabolic syndrome (odds ratio [OR] 8.28 [95% Cl 4.45-15.40]) than the obese (5.51 [2.81-10.80]) or sarcopenic group (2.64 [1.08-6.44]). CONCLUSIONS - SO defined by ASM/Wt was more closely associated with metabolic syndrome than either sarcopenia or obesity alone.Lim S, 2010, OBESITY, V18, P826, DOI 10.1038/oby.2009.232Stephen WC, 2009, J NUTR HEALTH AGING, V13, P460, DOI 10.1007/s12603-009-0084-zZamboni M, 2008, NUTR METAB CARDIOVAS, V18, P388, DOI 10.1016/j.numecd.2007.10.002Schrager MA, 2007, J APPL PHYSIOL, V102, P919, DOI 10.1152/japplphysiol.00627.2006Newman AB, 2006, J GERONTOL A-BIOL, V61, P72Janssen I, 2006, J AM GERIATR SOC, V54, P56, DOI 10.1111/j.1532-5415.2005.00540.xNair KS, 2005, AM J CLIN NUTR, V81, P953Baumgartner RN, 2004, OBES RES, V12, P1995Zoico E, 2004, INT J OBESITY, V28, P234, DOI 10.1038/sj.ijo.0802552Matsuzawa Y, 2002, CIRC J, V66, P987Janssen I, 2002, J AM GERIATR SOC, V50, P889Cleeman JI, 2001, JAMA-J AM MED ASSOC, V285, P2486, DOI 10.1001/jama.285.19.2486Baumgartner RN, 2000, ANN NY ACAD SCI, V904, P437*WHO W PAC REG, 2000, AS PAC PERSP RED OBSBaumgartner RN, 1998, AM J EPIDEMIOL, V147, P755

Determining the electronic performance limitations in top-down fabricated Si nanowires with mean widths down to 4 nm

Silicon nanowires have been patterned with mean widths down to 4 nm using top-down lithography and dry etching. Performance-limiting scattering processes have been measured directly which provide new insight into the electronic conduction mechanisms within the nanowires. Results demonstrate a transition from 3-dimensional (3D) to 2D and then 1D as the nanowire mean widths are reduced from 12 to 4 nm. The importance of high quality surface passivation is demonstrated by a lack of significant donor deactivation, resulting in neutral impurity scattering ultimately limiting the electronic performance. The results indicate the important parameters requiring optimization when fabricating nanowires with atomic dimensions

Generalized messengers of supersymmetry breaking and the sparticle mass spectrum

We investigate the sparticle spectrum in models of gauge-mediated supersymmetry breaking. In these models, supersymmetry is spontaneously broken at an energy scale only a few orders of magnitude above the electroweak scale. The breakdown of supersymmetry is communicated to the standard model particles and their superpartners by "messenger" fields through their ordinary gauge interactions. We study the effects of a messenger sector in which the supersymmetry-violating F-term contributions to messenger scalar masses are comparable to the supersymmetry-preserving ones. We also argue that it is not particularly natural to restrict attention to models in which the messenger fields lie in complete SU(5) GUT multiplets, and we identify a much larger class of viable models. Remarkably, however, we find that the superpartner mass parameters in these models are still subject to many significant contraints.Comment: 24 pages, LaTeX, uses epsf.sty, 4 figures. Assumptions clarified, numerical bounds tweaked, typos correcte

Field Theory And Second Renormalization Group For Multifractals In Percolation

The field-theory for multifractals in percolation is reformulated in such a way that multifractal exponents clearly appear as eigenvalues of a second renormalization group. The first renormalization group describes geometrical properties of percolation clusters, while the second-one describes electrical properties, including noise cumulants. In this context, multifractal exponents are associated with symmetry-breaking fields in replica space. This provides an explanation for their observability. It is suggested that multifractal exponents are ''dominant'' instead of ''relevant'' since there exists an arbitrary scale factor which can change their sign from positive to negative without changing the Physics of the problem.Comment: RevTex, 10 page

Pulse-shape discrimination between electron and nuclear recoils in a NaI(Tl) crystal

Abstract: We report on the response of a high light-output NaI(Tl) crystal to nuclear recoils induced by neutrons from an Am-Be source and compare the results with the response to electron recoils produced by Compton-scattered 662 keV γ-rays from a 137Cs source. The measured pulse-shape discrimination (PSD) power of the NaI(Tl) crystal is found to be significantly improved because of the high light output of the NaI(Tl) detector. We quantify the PSD power with a quality factor and estimate the sensitivity to the interaction rate for weakly interacting massive particles (WIMPs) with nucleons, and the result is compared with the annual modulation amplitude observed by the DAMA/LIBRA experiment. The sensitivity to spin-independent WIMP-nucleon interactions based on 100 kg·year of data from NaI detectors is estimated with simulated experiments, using the standard halo model. © 2015, The Author(s)1371Nsciescopu

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Diluted Networks of Nonlinear Resistors and Fractal Dimensions of Percolation Clusters

We study random networks of nonlinear resistors, which obey a generalized Ohm's law, $V\sim I^r$. Our renormalized field theory, which thrives on an interpretation of the involved Feynman Diagrams as being resistor networks themselves, is presented in detail. By considering distinct values of the nonlinearity r, we calculate several fractal dimensions characterizing percolation clusters. For the dimension associated with the red bonds we show that $d_{\scriptsize red} = 1/\nu$ at least to order {\sl O} (\epsilon^4), with $\nu$ being the correlation length exponent, and $\epsilon = 6-d$, where d denotes the spatial dimension. This result agrees with a rigorous one by Coniglio. Our result for the chemical distance, d_{\scriptsize min} = 2 - \epsilon /6 - [ 937/588 + 45/49 (\ln 2 -9/10 \ln 3)] (\epsilon /6)^2 + {\sl O} (\epsilon^3) verifies a previous calculation by one of us. For the backbone dimension we find D_B = 2 + \epsilon /21 - 172 \epsilon^2 /9261 + 2 (- 74639 + 22680 \zeta (3))\epsilon^3 /4084101 + {\sl O} (\epsilon^4), where $\zeta (3) = 1.202057...$, in agreement to second order in $\epsilon$ with a two-loop calculation by Harris and Lubensky.Comment: 29 pages, 7 figure

Effects of surfaces on resistor percolation

We study the effects of surfaces on resistor percolation at the instance of a semi-infinite geometry. Particularly we are interested in the average resistance between two connected ports located on the surface. Based on general grounds as symmetries and relevance we introduce a field theoretic Hamiltonian for semi-infinite random resistor networks. We show that the surface contributes to the average resistance only in terms of corrections to scaling. These corrections are governed by surface resistance exponents. We carry out renormalization group improved perturbation calculations for the special and the ordinary transition. We calculate the surface resistance exponents \phi_{\mathcal S \mathnormal} and \phi_{\mathcal S \mathnormal}^\infty for the special and the ordinary transition, respectively, to one-loop order.Comment: 19 pages, 3 figure