177,562 research outputs found
Canavan, R L, 2784719
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/375837Surname: CANAVAN
Given Name(s) or Initials: R L
Military Service Number or Last Known Location: 2784719
Missing, Wounded and Prisoner of War Enquiry Card Index Number: SEA-2689188538
Item: [2016.0049.08145] "Canavan, R L, 2784719
Severe retinal degeneration in a patient with Canavan disease
No full textBackground: Canavan disease is an autosomal recessive, neurodegenerative disorder caused by mutations in ASPA, a gene encoding the enzyme aspartoacylase. Patients present with macrocephaly, developmental delay, hypotonia, vision impairment and accumulation of N-acetylaspartic acid. Progressive white matter changes occur in the central nervous system. The disorder is often fatal in early childhood, but milder forms exist.
Materials and methods: Case report.
Results: We present the case of a 31-year-old male with mild/juvenile Canavan disease who had severe vision loss due to a retinal degeneration resembling retinitis pigmentosa. Prior to this case, vision loss in Canavan disease had been attributed to optic atrophy based on fundoscopic evidence of optic nerve pallor. Investigations for an alternative cause for our patient’s retinal degeneration were non-revealing.
Conclusion: We wonder if retinal degeneration may not have been previously recognized as a feature of Canavan disease. We highlight findings from animal models of Canavan disease to further support the association between Canavan disease and retinal degeneration
The potential for biological control on cryptic plant invasions
No full textCryptic invasions can be defined as ‘the occurrence of an invasive species or genotype that was not previously recognised as alien in origin or not distinguished from other aliens’. Such invasions can result in negative impacts on the recipient ecosystems and disturb the evolutionary history of native plant populations. Many cryptic invasions have become so problematic that there is a need to implement control measures. This paper explores the potential for biological control to be implemented as a means of managing cryptic invasions. Firstly, the paper defines the different forms of cryptic invasion, differentiating between interspecific and intraspecific invasions; this hierarchy influences how to detect, study and ultimately implement biological control when cryptic invasions occur. Secondly, unique challenges associated with biological control programmes for cryptic invasions are addressed, including: the need for intraspecific level host specificity in agents, the occurrence of hybridisation between native species/lineages and the target weed, the role of enemy release in cryptic invasions in the presence of closely related native plant species/lineages, and a review of potential stakeholder conflicts of interest and legislation. Biological control of cryptic invasions has been shown to be possible, however the process will be more difficult and complex than controlling traditional targets and will likely take up more time and resources. If these challenges are overcome, then biological control programmes against cryptic invasions should be able to proceed and maintain the same standards as traditional biological control programmes
Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan\u27s disease: a case report.
No full textThe neuroradiological evaluation of Canavan\u27s disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan\u27s disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan\u27s disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia: report of three cases in comparison with Canavan disease
No full textWe report three cases of L-2-hydroxyglutaric acidemia and three cases of Canavan disease. The L-2-hydroxyglutaric acidemia cases are the first biochemically proven Turkish cases. Magnetic resonance imaging findings in the cases and similarities between the two diseases are emphasized. Both diseases are characterized by predominant subcortical white-matter involvement and dentate nuclei lesions with variable basal ganglia involvement. Canavan disease differs from L-2-hydroxyglutaric acidemia by the presence of typical brainstem involvemen
Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy
No full textN-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease—a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation. We show that NAA-deficiency causes neurological deficits affecting unconscious defensive reactions aimed at protecting the body from external threat. This finding suggests, while NAA reduction is pivotal to treat Canavan disease, abrogating NAA synthesis should be avoided. At the other end of the spectrum, while predicting pathological severity in Canavan disease mice, increased brain NAA levels are not neurotoxic per se. In fact, in transgenic mice overexpressing the NAA synthesising enzyme Nat8l in neurons, supra-physiological NAA levels were uncoupled from neurological deficits. In contrast, elimination of aspartoacylase expression exclusively in oligodendrocytes elicited Canavan disease like pathology. Although conditional aspartoacylase deletion in oligodendrocytes abolished expression in the entire CNS, the remaining aspartoacylase in peripheral organs was sufficient to lower NAA levels, delay disease onset and ameliorate histopathology. However, comparable endpoints of the conditional and complete aspartoacylase knockout indicate that optimal Canavan disease gene replacement therapies should restore aspartoacylase expression in oligodendrocytes. On the basis of these findings we executed an ASPA gene replacement therapy targeting oligodendrocytes in Canavan disease mice resulting in reversal of pre-existing CNS pathology and lasting neurological benefits. This finding signifies the first successful post-symptomatic treatment of a white matter disorder using an adeno-associated virus vector tailored towards oligodendroglial-restricted transgene expression
„Człowiek Boże igrzysko” w trylogii Era Pięciorga Trudi Canavan
No full textW niniejszym szkicu analizie poddane zostają liczne reminiscencje mitologiczne w trylogii Era Pięciorga Trudi Canavan. Wyjątkowość tego cyklu powieściowego polega bowiem na tym, że w całości traktuje on o bogach i religii. Zestawione ze sobą zostają dwa zaskakująco podobne systemy dogmatyczne stworzone przez autorkę. Przedstawiciele cyrklianizmu i pentedrianizmu toczą ze sobą wojny na tle religijnym. Okazuje się jednak, iż są manipulowani przez obiekty swoich kultów. W rzeczywistości oddają bowiem cześć tym samym bogom, którzy znudzeni wiecznością toczą ze sobą okrutną partię szachów, w której pionkami są ich wyznawcy, szachownicą zaś cały świat. Przedstawiona fabuła jest pretekstem do stawiania trudnych pytań o rolę i celowość religii w życiu człowieka, o sens wierności przekonaniom, o niezmienne, ponadczasowe wartości.This article contains an analysis of numerous reminiscences of mythological paradigm in Age of the Five trilogy by Trudi Canavan. The particularity of the cycle is that it is devoted – in its entirety – to religion theme. It juxtaposes two surprisingly similar dogmatic systems created by Canavan. Circlians and pentedrians fight each other on religious ground. However, as it appears, they are actually manipulated by the objects of their worship. Bored gods play a cruel game of chess where their followers become mere pawns. The story is a starting point to ask difficult questions about the role and relevance of religion in human life, about loyalty to the principles, and other timeless values.Małgorzata Antuszewicz – urodzona w 1979; nauczycielka języka polskiego w Zespole Szkół w Rotmance (niedaleko Pruszcza Gdańskiego); magister filologii polskiej; doktorantka Uniwersytetu Gdańskiego; autorka artykułów: Uczniowska recepcja II części „Dziadów” („Język – Szkoła – Religia”, R. VII, nr 2, Pelplin 2012), Recepcja romantyzmu i zdziwienie szczególne (artykuł w druku).20321
A new mouse model of Canavan leukodystrophy displays hearing impairment due to central nervous system dysmyelination
No full textCanavan disease is a leukodystrophy caused by mutations in the ASPA gene. This gene encodes the enzyme that converts N-acetylaspartate into acetate and aspartic acid. In Canavan disease, spongiform encephalopathy of the brain causes progressive mental retardation, motor deficit and death. We have isolated a mouse with a novel ethylnitrosourea-induced mutation in Aspa. This mutant, named deaf14, carries a c.516T>A mutation that is predicted to cause a p.Y172X protein truncation. No full-length ASPA protein is produced in deaf14 brain and there is extensive spongy degeneration. Interestingly, we found that deaf14 mice have an attenuated startle in response to loud noise. The first auditory brainstem response peak has normal latency and amplitude but peaks II, III, IV and V have increased latency and decreased amplitude in deaf14 mice. Our work reveals a hitherto unappreciated pathology in a mouse model of Canavan disease, implying that auditory brainstem response testing could be used in diagnosis and to monitor the progression of this disease.Marina R. Carpinelli, Anne K. Voss, Michael G. Manning, Ashwyn A. Perera, Anne A. Cooray, Benjamin T. Kile and Rachel A. Bur
Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy
No full textN-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease-a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation. We show that NAA-deficiency causes neurological deficits affecting unconscious defensive reactions aimed at protecting the body from external threat. This finding suggests, while NAA reduction is pivotal to treat Canavan disease, abrogating NAA synthesis should be avoided. At the other end of the spectrum, while predicting pathological severity in Canavan disease mice, increased brain NAA levels are not neurotoxic per se. In fact, in transgenic mice overexpressing the NAA synthesising enzyme Nat8l in neurons, supra-physiological NAA levels were uncoupled from neurological deficits. In contrast, elimination of aspartoacylase expression exclusively in oligodendrocytes elicited Canavan disease like pathology. Although conditional aspartoacylase deletion in oligodendrocytes abolished expression in the entire CNS, the remaining aspartoacylase in peripheral organs was sufficient to lower NAA levels, delay disease onset and ameliorate histopathology. However, comparable endpoints of the conditional and complete aspartoacylase knockout indicate that optimal Canavan disease gene replacement therapies should restore aspartoacylase expression in oligodendrocytes. On the basis of these findings we executed an ASPA gene replacement therapy targeting oligodendrocytes in Canavan disease mice resulting in reversal of pre-existing CNS pathology and lasting neurological benefits. This finding signifies the first successful post-symptomatic treatment of a white matter disorder using an adeno-associated virus vector tailored towards oligodendroglial-restricted transgene expression
- …
