Silencing mutant ataxin-3 rescues motor deficits and neuropathology in machado-joseph disease transgenic mice.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene. This expansion translates into a polyglutamine tract that confers a toxic gain-of-function to the mutant protein - ataxin-3, leading to neurodegeneration in specific brain regions, with particular severity in the cerebellum. No treatment able to modify the disease progression is available. However, gene silencing by RNA interference has shown promising results. Therefore, in this study we investigated whether lentiviral-mediated allele-specific silencing of the mutant ataxin-3 gene, after disease onset, would rescue the motor behavior deficits and neuropathological features in a severely impaired transgenic mouse model of MJD. For this purpose, we injected lentiviral vectors encoding allele-specific silencing-sequences (shAtx3) into the cerebellum of diseased transgenic mice expressing the targeted C-variant of mutant ataxin-3 present in 70% of MJD patients. This variation permits to discriminate between the wild-type and mutant forms, maintaining the normal function of the wild-type allele and silencing only the mutant form. Quantitative analysis of rotarod performance, footprint and activity patterns revealed significant and robust alleviation of gait, balance (average 3-fold increase of rotarod test time), locomotor and exploratory activity impairments in shAtx3-injected mice, as compared to control ones injected with shGFP. An important improvement of neuropathology was also observed, regarding the number of intranuclear inclusions, calbindin and DARPP-32 immunoreactivity, fluorojade B and Golgi staining and molecular and granular layers thickness. These data demonstrate for the first time the efficacy of gene silencing in blocking the MJD-associated motor-behavior and neuropathological abnormalities after the onset of the disease, supporting the use of this strategy for therapy of MJD

Bias driven coherent carrier dynamics in a two-dimensional aperiodic potential

We study the dynamics of an electron wave-packet in a two-dimensional square lattice with an aperiodic site potential in the presence of an external uniform electric field. The aperiodicity is described by $\epsilon_{\bf m} = V\cos{(\pi\alpha m_x^{\nu_x})}\cos{(\pi\alpha m_y^{\nu_y})}$ at lattice sites $(m_x, m_y)$, with $\pi \alpha$ being a rational number, and $\nu_x$ and $\nu_y$ tunable parameters, controlling the aperiodicity. Using an exact diagonalization procedure and a finite-size scaling analysis, we show that in the weakly aperiodic regime ($\nu_x,\nu_y < 1$), a phase of extended states emerges in the center of the band at zero field giving support to a macroscopic conductivity in the thermodynamic limit. Turning on the field gives rise to Bloch oscillations of the electron wave-packet. The spectral density of these oscillations may display a double peak structure signaling the spatial anisotropy of the potential landscape. The frequency of the oscillations can be understood using a semi-classical approach.Comment: 16 pages, to appear in Phys. Lett.

Condensed matter and AdS/CFT

I review two classes of strong coupling problems in condensed matter physics, and describe insights gained by application of the AdS/CFT correspondence. The first class concerns non-zero temperature dynamics and transport in the vicinity of quantum critical points described by relativistic field theories. I describe how relativistic structures arise in models of physical interest, present results for their quantum critical crossover functions and magneto-thermoelectric hydrodynamics. The second class concerns symmetry breaking transitions of two-dimensional systems in the presence of gapless electronic excitations at isolated points or along lines (i.e. Fermi surfaces) in the Brillouin zone. I describe the scaling structure of a recent theory of the Ising-nematic transition in metals, and discuss its possible connection to theories of Fermi surfaces obtained from simple AdS duals.Comment: 39 pages, 12 figures; Lectures at the 5th Aegean summer school, "From gravity to thermal gauge theories: the AdS/CFT correspondence", and the De Sitter Lecture Series in Theoretical Physics 2009, University of Groninge

Ácido cianídrico em tecidos de mandioca em função da idade da planta e adubação nitrogenada

O objetivo deste trabalho foi avaliar o teor de ácido cianídrico em tecidos de mandioca, em função da idade da planta e níveis de adubação nitrogenada. Utilizou-se o delineamento experimental de blocos ao acaso, em arranjo de parcelas subdivididas, com quatro repetições. As doses de nitrogênio em cobertura (0, 30, 60, 150 e 330 kg ha-1) foram alocadas nas parcelas, e as épocas de avaliação (90, 120, 150, 180, 240, 300 e 360 dias após o plantio), nas subparcelas. Os teores de ácido cianídrico foram avaliados em tecidos da folha, caule, polpa e córtex da raiz da cultivar Aciolina. Os efeitos das doses de N e das épocas de avaliação foram independentes. Doses entre 219 e 241 kg ha-1 de N em cobertura proporcionam os maiores teores de ácido cianídrico, que variaram de 332 a 401 mg kg-1 de matéria fresca nos tecidos avaliados. O teor de ácido cianídrico nos tecidos reduz-se linearmente com a idade da planta. O córtex da raiz acumula o maior teor de ácido cianídrico, e a polpa da raiz o menor. Por ocasião da colheita, aos 360 dias após o plantio, essa cultivar é classificada como mandioca mansa

Acúmulo de carbono em Latossolo adubado com dejeto líquido de suínos e cultivado em plantio direto

O objetivo deste trabalho foi estimar taxas de acúmulo de C orgânico em Latossolo Vermelho adubado com adubo solúvel e dejeto líquido de suíno e cultivado em plantio direto. O experimento foi conduzido em Campos Novos, SC, e os seguintes tratamentos foram aplicados anualmente: sem adubação; adubo solúvel; 25 m3 ha-1 de dejeto líquido + adubo solúvel; e doses de 25, 50, 100 e 200 m3 ha-1 de dejeto líquido. Foram determinados: os estoques de C orgânico (CO) na camada de 0-20 cm do solo; a adição de C pela fitomassa dos cultivos e pelo dejeto líquido de suíno; as taxas anuais de fixação de C; e os coeficientes de humificação (k1) e de mineralização (k2) de CO do solo. As taxas de fixação de C real e aparente aumentaram de acordo com as doses de dejeto, tendo variado de 0,6 a 1,7 e de 0,05 a 1,0 Mg ha-1 por ano, respectivamente. Os coeficientes k1 e k2 foram 0,17 e 0,011, respectivamente, enquanto o aporte de C requerido para manter o estoque inicial de CO do solo é de 4,14 Mg ha-1 por ano. O dejeto líquido de suíno aplicado anualmente em Latossolo Vermelho cultivado com a sucessão milho-aveia-preta em plantio direto aumenta o CO do solo em doses de até 200 m3 ha-1