SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease.

International audience; Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system's functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD

SINEUP non-coding RNA activity depends on specific N6-methyladenosine nucleotides

: SINEUPs are natural and synthetic antisense long non-coding RNAs (lncRNAs) selectively enhancing target mRNAs translation by increasing their association with polysomes. This activity requires two RNA domains: an embedded inverted SINEB2 element acting as effector domain, and an antisense region, the binding domain, conferring target selectivity. SINEUP technology presents several advantages to treat genetic (haploinsufficiencies) and complex diseases restoring the physiological activity of diseased genes and of compensatory pathways. To streamline these applications to the clinic, a better understanding of the mechanism of action is needed. Here we show that natural mouse SINEUP AS Uchl1 and synthetic human miniSINEUP-DJ-1 are N6-methyladenosine (m6A) modified by METTL3 enzyme. Then, we map m6A-modified sites along SINEUP sequence with Nanopore direct RNA sequencing and a reverse transcription assay. We report that m6A removal from SINEUP RNA causes the depletion of endogenous target mRNA from actively translating polysomes, without altering SINEUP enrichment in ribosomal subunit-associated fractions. These results prove that SINEUP activity requires an m6A-dependent step to enhance translation of target mRNAs, providing a new mechanism for m6A translation regulation and strengthening our knowledge of SINEUP-specific mode of action. Altogether these new findings pave the way to a more effective therapeutic application of this well-defined class of lncRNAs

Quantum walk on distinguishable non-interacting many-particles and indistinguishable two-particle

We present an investigation of many-particle quantum walks in systems of non-interacting distinguishable particles. Along with a redistribution of the many-particle density profile we show that the collective evolution of the many-particle system resembles the single-particle quantum walk evolution when the number of steps is greater than the number of particles in the system. For non-uniform initial states we show that the quantum walks can be effectively used to separate the basis states of the particle in position space and grouping like state together. We also discuss a two-particle quantum walk on a two- dimensional lattice and demonstrate an evolution leading to the localization of both particles at the center of the lattice. Finally we discuss the outcome of a quantum walk of two indistinguishable particles interacting at some point during the evolution.Comment: 8 pages, 7 figures, To appear in special issue: "quantum walks" to be published in Quantum Information Processin

Quantum walks: a comprehensive review

Quantum walks, the quantum mechanical counterpart of classical random walks, is an advanced tool for building quantum algorithms that has been recently shown to constitute a universal model of quantum computation. Quantum walks is now a solid field of research of quantum computation full of exciting open problems for physicists, computer scientists, mathematicians and engineers. In this paper we review theoretical advances on the foundations of both discrete- and continuous-time quantum walks, together with the role that randomness plays in quantum walks, the connections between the mathematical models of coined discrete quantum walks and continuous quantum walks, the quantumness of quantum walks, a summary of papers published on discrete quantum walks and entanglement as well as a succinct review of experimental proposals and realizations of discrete-time quantum walks. Furthermore, we have reviewed several algorithms based on both discrete- and continuous-time quantum walks as well as a most important result: the computational universality of both continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing Journa

Voces abiertas : comunicación, política y ciudadanía en América Latina

En un contexto donde las academias, los organismos internacionales y los diferentes Estados enuncian y denuncian la llamada crisis del neoliberalismo o modelo capitalista, emergen en América Latina en especial en el Cono Sur gobiernos comprometidos con la democracia con el despliegue de políticas de inclusión social y económica y con la integración social, política, económica y cultural. Entre sus medidas principales y prioritarias se encuentra una serie de normativas y políticas tendientes a regular los sistemas info-comunicacionales en pos de una distribución más justa de la palabra y de garantizar el derecho de los pueblos a la comunicación

Quantum logic using correlated one-dimensional quantum walks

Quantum computing through quantum walks The behavior of quantum particles walking on a lattice can be exploited to design quantum gates. Quantum gates, which are the building blocks of a general purpose quantum computer, are typically designed in easy to model physical systems where the necessary behavior for the gate operation can be explicitly written out. In contrast, a collaboration between the Physics and Electrical Engineering departments at MIT has shown that the behavior of much more complicated quantum systems can be engineered, with the aid of numerical optimization, to perform the full set of necessary operations for a quantum computer. This insight expands the range of platforms that could be useful for quantum information processing, helping push towards the realization of a general purpose quantum computer