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.

Incidência natural e biologia de Trichogramma atopovirilia Oatman & Platner, 1983 (Hymenoptera, Trichogrammatidae) em ovos de Anticarsia gemmatalis Hübner, 1818 (Lepidoptera, Noctuidae)

Trichogramma atopovirilia Oatman & Platner is an egg parasitoid of the corn earworm Helicoverpa zea (Boddie) (Lepidoptera, Noctuidae), and has recently been collected from eggs of Anticarsia gemmatalis Hübner on soybeans. In order to evaluate the suitability of A. gemmatalis eggs as hosts of T. atopovirilia, field surveys were conducted in 1999 and 2000 on corn and soybeans, and a colony of the parasitoid was established in laboratory. At 25 ºC, development from oviposition to emergence lasted nine days and a sex-ratio of 0.58 (females:males) was obtained. Females lived significantly longer (11.4 days) when kept in ovipositional activity, than in the absence of host eggs (6.6 days). Total fecundity averaged 104.5 parasitized eggs, resulting in the emergence of 138.3 descendents. Mean daily fecundity was highest (30 eggs/female) on the first day. Oviposition continued until one day before the death of the females, however 70% of the eggs were laid during the first four days after emergence. A female-biased progeny was produced during the first three days of oviposition, whereas further ovipositions were male-biased. Females lived significantly longer when exposed to host eggs in comparison to females deprived of eggs. The results show that eggs of A. gemmatalis are suitable for the development of T. atopovirilia, and this parasitoid should be considered in future programs of biological control of the velvetbean caterpillar.

Uma nova espécie de Strebla Wiedemann, 1824 (Diptera, Streblidae, Streblinae) sobre Anoura caudifer (E. Geoffroy, 1818) (Chiroptera, Phyllostomidae, Glossophaginae)

A new species of Strebla Wiedemann, S. carvalhoi sp. nov., collected, on Anoura caudifer (E. Geoffroy, 1818) from Southern of Brazil, is described. Drawings of the postvertex, occipital plates, gonopods and tergite VII are provided.