Golgi Outpost Synthesis Impaired by Toxic Polyglutamine Proteins Contributes to Dendritic Pathology in Neurons

Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA, which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway. ? 2017 The Author(s)113Ysciescopu

Probabilistic reasoning with a bayesian DNA device based on strand displacement

We present a computing model based on the DNA strand displacement technique which performs Bayesian inference. The model will take single stranded DNA as input data, representing the presence or absence of a specific molecular signal (evidence). The program logic encodes the prior probability of a disease and the conditional probability of a signal given the disease playing with a set of different DNA complexes and their ratios. When the input and program molecules interact, they release a different pair of single stranded DNA species whose relative proportion represents the application of Bayes? Law: the conditional probability of the disease given the signal. The models presented in this paper can empower the application of probabilistic reasoning in genetic diagnosis in vitro

Search for Λc+→pK+π−\Lambda_c^+ \to p K^+ \pi^- and Ds+→K+K+π−D_s^+ \to K^+ K^+ \pi^- Using Genetic Programming Event Selection

We apply a genetic programming technique to search for the double Cabibbo suppressed decays $\Lambda_c^+ \to p K^+ \pi^-$ and $D_s^+ \to K^+ K^+ \pi^-$. We normalize these decays to their Cabibbo favored partners and find $\text{BR}($\Lambda_c^+ \to p K^+ \pi^-$)/\text{BR}($\Lambda_c^+ \to p K^- \pi^+$) = (0.05 \pm 0.26 \pm 0.02)$ and $\text{BR}($D_s^+ \to K^+ K^+ \pi^-$)/\text{BR}($D_s^+ \to K^+ K^- \pi^+$) = (0.52\pm 0.17\pm 0.11)$ where the first errors are statistical and the second are systematic. Expressed as 90% confidence levels (CL), we find $< 0.46$ and $< 0.78$ respectively. This is the first successful use of genetic programming in a high energy physics data analysis.Comment: 10 page

Measurement of the D+ and Ds+ decays into K+K-K+

We present the first clear observation of the doubly Cabibbo suppressed decay D+ --> K-K+K+ and the first observation of the singly Cabibbo suppressed decay Ds+ --> K-K+K+. These signals have been obtained by analyzing the high statistics sample of photoproduced charm particles of the FOCUS(E831) experiment at Fermilab. We measure the following relative branching ratios: Gamma(D+ --> K-K+K+)/Gamma(D+ --> K-pi+pi+) = (9.49 +/- 2.17(statistical) +/- 0.22(systematic))x10^-4 and Gamma(Ds+ --> K-K+K+)/Gamma(Ds+ --> K-K+pi+) = (8.95 +/- 2.12(statistical) +2.24(syst.) -2.31(syst.))x10^-3.Comment: 10 pages, 8 figure

A Non-parametric Approach to the D+ to K*0bar mu+ nu Form Factors

Using a large sample of D+ -> K- pi+ mu+ nu decays collected by the FOCUS photoproduction experiment at Fermilab, we present the first measurements of the helicity basis form factors free from the assumption of spectroscopic pole dominance. We also present the first information on the form factor that controls the s-wave interference discussed in a previous paper by the FOCUS collaboration. We find reasonable agreement with the usual assumption of spectroscopic pole dominance and measured form factor ratios.Comment: 14 pages, 5 figures, and 2 tables. We updated the previous version by changing some words, removing one plot, and adding two tables. These changes are mostly stylisti

Measurements of Ξc+\Xi_c^{+} Branching Ratios

Using data collected by the fixed target Fermilab experiment FOCUS, we measure the branching ratios of the Cabibbo favored decays $\Xi_c^+ \to \Sigma^+K^-\pi^+$, $\Xi_c^+ \to \Sigma^+ \bar{K}^{*}(892)^0$, and $\Xi_c^+ \to \Lambda^0K^-\pi^+\pi^+$ relative to $\Xi_c^+ \to \Xi^-\pi^+\pi^+$ to be $0.91\pm0.11\pm0.04$, $0.78\pm0.16\pm0.06$, and $0.28\pm0.06\pm0.06$, respectively. We report the first observation of the Cabibbo suppressed decay $\Xi_c^+ \to \Sigma^+K^+K^-$ and we measure the branching ratio relative to $\Xi_c^+ \to \Sigma^+K^-\pi^+$ to be $0.16\pm0.06\pm0.01$. We also set 90% confidence level upper limits for $\Xi_c^+ \to \Sigma^+ \phi$ and $\Xi_c^+ \to \Xi^*(1690)^0(\Sigma^+ K^-) K^+$ relative to $\Xi_c^+ \to \Sigma^+K^-\pi^+$ to be 0.12 and 0.05, respectively. We find an indication of the decays $\Xi_c^+ \to \Omega^-K^{+}\pi^+$ and $\Xi_c^+ \to \Sigma^{*}(1385)^+ \bar{K}^0$ and set 90% confidence level upper limits for the branching ratios with respect to $\Xi_c^+ \to \Xi^-\pi^+\pi^+$ to be 0.12 and 1.72, respectively. Finally, we determine the 90% C.L. upper limit for the resonant contribution $\Xi_c^+ \to \Xi^{*}(1530)^0 \pi^+$ relative to $\Xi_c^+ \to \Xi^-\pi^+\pi^+$ to be 0.10.Comment: 14 pages, 8 figure

Dalitz plot analysis of D_s+ and D+ decay to pi+pi-pi+ using the K-matrix formalism

FOCUS results from Dalitz plot analysis of D_s+ and D+ to pi+pi-pi+ are presented. The K-matrix formalism is applied to charm decays for the first time to fully exploit the already existing knowledge coming from the light-meson spectroscopy experiments. In particular all the measured dynamics of the S-wave pipi scattering, characterized by broad/overlapping resonances and large non-resonant background, can be properly included. This paper studies the extent to which the K-matrix approach is able to reproduce the observed Dalitz plot and thus help us to understand the underlying dynamics. The results are discussed, along with their possible implications on the controversial nature of the sigma meson.Comment: To be submitted to Phys.Lett.B A misprint corrected in formula

Measurement of the branching ratio of the decay D^0 -> \pi^-\mu^+\nu relative to D^0 -> K^-\mu^+\nu

We present a new measurement of the branching ratio of the Cabibbo suppressed decay D^0\to \pi^-\mu^+\nu relative to the Cabibbo favored decay D^0\to K^-\mu^+\nu and an improved measurement of the ratio |\frac{f_+^{\pi}(0)}{f_+^{K}(0)}|. Our results are 0.074 \pm 0.008 \pm 0.007 for the branching ratio and 0.85 \pm 0.04 \pm 0.04 \pm 0.01 for the form factor ratio, respectively.Comment: 13pages, 3 figure

Study of Hadronic Five-Body Decays of Charmed Mesons

We study the decay of D+ and Ds+ mesons into charged five body final states, and report the discovery of the decay mode D+ -> K+K-Pi+Pi+Pi-, as well as measurements of the decay modes D+ -> K-Pi+Pi+Pi+Pi-, Ds+ -> K+K-Pi+Pi+Pi-, Ds+ -> PhiPi+Pi+Pi- and D+/Ds+ -> Pi+Pi+Pi+Pi-Pi-. An analysis of the resonant substructure is also included, with evidence suggesting that both decays proceed primarily through an a1 vector resonance.Comment: 11 pages, 3 figure

New Measurements of the D+ to K* mu nu Form Factor Ratios

Using a large sample of D+ to K- pi+ mu+ nu decays collected by the FOCUS photoproduction experiment at Fermilab, we present new measurements of two semileptonic form factor ratios: rv and r2. We find rv = 1.504 \pm 0.057 \pm 0.039 and r2 = 0.875 \pm 0.049 \pm 0.064. Our form factor results include the effects of the s-wave interference discussed in a previous paper.Comment: 12 pages, 5 figure