997 resultados para Joseph West
Resumo:
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.
Resumo:
To evaluate the risk of transmission of vector-borne diseases, regular updates of the geographic distribution of insect vectors are required. In the archipelago of Cape Verde, nine mosquito species have been reported. Of these, four are major vectors of diseases that have been present in the archipelago: yellow fever, lymphatic filariasis, malaria and, currently, an outbreak of dengue. In order to assess variation in mosquito biodiversity, we have carried out an update on the distribution of the mosquito species in Cape Verde, based on an enquiry of 26 unpublished technical reports (1983-2006) and on the results of an entomological survey carried out in 2007. Overall, there seems to be a general trend for an expansion of biological diversity in the islands. Mosquito species richness was negatively correlated with the distance of the islands from the mainland but not with the size of the islands. Human- and/or sporadic climatic-mediated events of dispersal may have contributed to a homogenization of species richness regardless of island size but other ecological factors may also have affected the mosquito biogeography in the archipelago. An additional species, Culex perexiguus, was collected for the first time in the archipelago during the 2007 survey.
Resumo:
Many species of Apiaceae are found in the Macaronesien Region. Several have been introduccd by human activities, but a number of taxa is endemic to the different archipelagos or even rrstrictcd to a single island. The following enumeration is based mainly on HANSEN & SUNDING ( 1993). In the Arores 28 different taxa of Apiaceae occur; among them four endemic species [AUIMI; hrrrrii WATSON, A. trifoliatum (WATSON) TKEL., Clrtrc~,y~l~~ll~r~~~ cl:oricrm TREL.. SOErich trwrictr GUTIINICK ex SEUB.]. In Madeira the Apiaceae are very diverse and consist ol’ 29 species and subspecies. From the archipelago two monotypic genera, rC/c/trtio. velitru~rr t/ccipicvr.s (SCHRAD. & J. C. WENDL.) Ho~+hl. md kJorli:ia edu[is LOWE and ~hrcc cndcmic species [Oemmrlre diwricore (R. BR.) MABB.. I/nperrr/orio lotvei COSS. and Burrirr~r hre~$~lirrnr LOWE] are described. The Canary Islands have the highest numbcr of plant-species and a high level of endemism. 5-l taxa of Apiaceae are recorded including three endemic genera (Rtrrheopsis A. HANSEX & KUNKEL, Todm-oa PARL. and Tiqyrmm PARL.) and further I5 endemic taxa. The Apiaceae are represented in the Cape Verde Islands by I2 species. Most of the taxa have been introduced by human activities (LOBIN & ZIZKA 1957) like Amvhm grm’eo- 1efr.s L., Apirm grmvolerrs L, Foerricrrhrr urlgore MILL.. Corimrtlru~t~ srrtirvrrrr L. or Petrosilerrm crisprrm (FRILL.) A.W.HILL. These species are cultivated and some of them later became \\esdy. Other species like Ciclosper- UWL /e/~fo/~/l~ll~rrtr (PER%) SPRAGUE (= Apimr leproplr~llrr~rr) are weeds of cultivated grounds or wasted lands. All these species are today widespread in temperate. subtropical or tropical regions all over the world. The only native species are to be found in the endemic genus To~wI~~I~~~ PARL.
Resumo:
Water fact sheet for Iowa Department of Natural Resources and the Geological Bureau.
Resumo:
Does the labor market place wage premia on jobs that involve physical strain,job, insecurity or bad regulation of hours? This paper derives bounds on themonetary returns to these job disamenities in the West German labor market.We show that in a market with dispersion in both job characteristics andwages, the average wage change of workers who switch jobs voluntarily and optfor consuming more (less) disamenities,provides an upper (lower) bound on themarket return to the disamenity. Using longitudinal information from workersin the German Socio Economic Panel, we estimate an upper bound of 5% and alower bound of 3.5% for the market return to work strain in a job.
Resumo:
Audit report on the City of West Branch, Iowa for the year ended June 30, 2007