The botany of the Antarctic voyage of H.M. discovery ships Erebus and Terror in the Years 1839-1843 :under the command of Captain Sir James Clark Ross /by Joseph Dalton Hooker.

v.1 Text (1844)

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.

[4 phot. des monuments élevés par Jean Joseph de La Borde dans le parc de son château de Méréville (Seine-et-Oise), à la fin du XVIIIe siècle, à la mémoire de ses deux fils, de La Borde-Marchainville et de La Borde-Boutervilliers, officiers de l'Astrolabe, péris avec La Pérouse en 1786, ainsi qu'à la mémoire du capitaine Cook, don du prince Roland Bonaparte en 1896. Voir les CR. des séances de la S.G., 1896, p. 319-321]

Donateur : Bonaparte, Roland (1858-1924)

RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of machado-joseph disease.

Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allele-specific silencing for therapy of this disease.

Travels through Sweden, Finland, and Lapland, to the North Cape, in the years 1798 and 1799 : by Joseph Acerbi. In two volumes. Illustrated with seventeen elegant engravings. Vol. I[-II].

Vol. I: Portrait of Joseph Acerbi. Painted by P. Violet, engr. by P. W. Tomkins.

Travels through Sweden, Finland, and Lapland, to the North Cape, in the years 1798 and 1799 : by Joseph Acerbi. In two volumes. Illustrated with seventeen elegant engravings. Vol. I[-II].

Vol. I: Portrait of Joseph Acerbi. Painted by P. Violet, engr. by P. W. Tomkins.

Benjamin Woodruff Price Papers, 1851, 1853-1860, 1862-1863, 1874, n.d.

The fonds includes sixty two items of correspondence between Benjamin Woodruff Price, aka Woodruff, Ben or Uncle, and various family members, both immediate and distant cousins. Also included is business correspondence related to Price’s activities as a watchmaker and/or jeweler. Benjamin Woodruff Price was born in Thorold Township ca. 1831, the son of Joseph Price and Mary Smith. B.W. Price married Ella or Ellen McGlashan (1851-1906) ca. 1868. Price died between 1891 and 1901, his burial location is unknown at present. A watchmaker and jeweler, Price lived most of his life in Fonthill, Ont. He also included auctioneer, undertaker and photographer as some of his other professional activities. His siblings included David Smith Price (wife Isabella Ann), John Smith Price (wife Elizabeth Jane), and sisters Susan Page (husband Edward Rice Page), Jerusha Price, Mary Price and Martha W. Stone (husband Dudley Ward Stone). John Smith Price died 18 April 1860, leaving no descendents. It is likely that G.W. Stone was a nephew to B.W. Price, the son of his sister Martha W. Stone and her husband Dudley Ward Stone. Susan Page was a sister of Benjamin Woodruff Price. She was married to Edward Rice Page and they had at least two children, Joseph and Clayton. At the time of this correspondence they lived in Suspension Bridge, NY, now part of Niagara Falls, New York. Edward Rice Page’s occupation was listed as saloon keeper. The Price family appears to have had a very large extended family. This information was gleaned from the contents of letters of Maggie Tisdale, daughter of Ephraim and Hannah (Price) Tisdale, P.A. or Ann Morgan, [may also be Phebe Ann] of Newark, NY? and Marietta House of Bayham Township. DeWitt Higgins of Suspension Bridge, NY aka Niagara Falls, NY was an auctioneer, specialized in buying jewellery, watches, clocks, from individuals and reselling his product to others like B.W. Price.

Daguerreotype - Joseph Woodruff

Daguerreotype, 12 cm x 9 cm of Joseph Woodruff. The daguerreotype is slightly pitted and it is enclosed in a frame. This is accompanied by a note written by R. W. Band.