1,255 research outputs found
A Simple and Reliable Reporter Assay to Test siRNA-Mediated Silencing of HIV-1 Gene Functions
The human immunodeficiency virus (HIV-1) infects and kills CD4+ T-lymphocytes causing a progressive loss of host immune competence, which ultimately leads to AIDS. RNA interference, as mediated by short interfering RNAs (siRNAs) designed to target viral mRNAs and expressed endogenously, offer a potential gene therapy approach to inhibit HIV replication. However, a simple and reliable method to screen the silencing activity of particular anti-HIV siRNAs is useful prior to conducting more extensive experimentation to determine the downstream effects on viral replication. Here, a short hairpin RNA (shRNA) targeting HIV-1 Rev (Revsh8526) was designed and cloned into an expression plasmid under the control of the RNA Polymerase III H1 promoter. To test the ability of Revsh8526 to silence Rev, a chimeric β-galactosidase reporter plasmid containing Rev exon 2 (β-galactosidase-RevE2) was generated. The ability of Revsh8526 to target and inhibit reporter gene expression was shown by X-gal staining and ortho-nitrophenyl-β-galactoside (ONPG) assay. The results of these assays indicated Revsh8526 effectively targeted and significantly inhibited β-galactosidase expression as compared to a non-targeted shRNA. These results show the utility of the chimeric β-galactosidase reporter in initial screening of siRNA reagents
Memory, learning and language in autism spectrum disorder
Background and aims: The âdual-systemsâ model of language acquisition has been used by Ullman and colleagues to explain patterns of strength and weakness in the language of higher-functioning people with autism spectrum disorder (ASD). Specifically, intact declarative/explicit learning is argued to compensate for a deficit in non-declarative/implicit procedural learning, constituting an example of the so-called âsee-sawâ effect. Ullman and Pullman (2015) extended their argument concerning a see-saw effect on language in ASD to cover other perceived anomalies of behaviour, including impaired acquisition of social skills. The aim of this paper is to present a critique of Ullman and colleaguesâ claims, and to propose an alternative model of links between memory systems and language in ASD.
Main contribution: We argue that a 4-systems model of learning, in which intact semantic and procedural memory are used to compensate for weaknesses in episodic memory and perceptual learning, can better explain patterns of language ability across the autistic spectrum. We also argue that attempts to generalise the âimpaired implicit learning/spared declarative learningâ theory to other behaviours in ASD are unsustainable.
Conclusions: Clinically significant language impairments in ASD are under-researched, despite their impact on everyday functioning and quality of life. The relative paucity of research findings in this area lays it open to speculative interpretation which may be misleading.
Implications: More research is need into links between memory/learning systems and language impairments across the spectrum. Improved understanding should inform therapeutic intervention, and contribute to investigation of the causes of language impairment in ASD with potential implications for prevention
Language and theory of mind in autism spectrum disorder : the relationship between complement syntax and false belief task performance.
This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of âhacking outâ solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a âmemory for complementsâ task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered
Defining language impairments in a subgroup of children with autism spectrum disorder
Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH
Failure to learn from feedback underlies word learning difficulties in toddlers at risk for autism
Childrenâs assignment of novel words to nameless objects, over objects
whose names they know (mutual exclusivity; ME) has been described
as a driving force for vocabulary acquisition. Despite their ability to use
ME to fast-map words (Preissler & Carey, 2005), children with autism
show impaired language acquisition. We aimed to address this puzzle
by building on studies showing that correct referent selection using
ME does not lead to word learning unless ostensive feedback is
provided on the childâs object choice (Horst & Samuelson, 2008). We
found that although toddlers aged 2;0 at risk for autism can use ME to
choose the correct referent of a word, they do not benefit from feedback
for long-term retention of the wordâobject mapping. Further, their
difficulty using feedback is associated with their smaller receptive
vocabularies. We propose that difficulties learning from social feedback,
not lexical principles, limits vocabulary building during development
in children at risk for autism
Using question words or asking yes/no questions: Failure and success in clarifying the intentions of a boy with highâfunctioning autism
Reimagining liver transplantation in South Africa: A model for justice equity and capacity building ââŹâ the Wits Donald Gordon Medical Centre experience
The challenge of providing effective and integrated liver transplant services across South AfricaââŹâ˘s two socioeconomically disparate healthcare sectors has been faced by Wits Donald Gordon Medical Centre (WDGMC) since 2004. WDGMC is a private academic hospital in Johannesburg and serves to supplement the specialist and subspecialist medical training provided by the University of the Witwatersrand. Over the past 14 years, our liver transplant programme has evolved from a sometimes fractured service into the largest-volume liver centre in sub-Saharan Africa. The growth of our programme has been the result of a number of innovative strategies tailored to the unique nature of transplant service provision. These include an employment model for doctors, a robust training and research programme, and a collaboration with the Gauteng Department of Health (GDoH) that allows us to provide liver transplantation to state sector patients and promotes equality. We have also encountered numerous challenges, and these continue, especially in our endeavour to make access to liver transplantation equitable but also an economically viable option for our hospital. In this article, we detail the liver transplant model at WDGMC, fully outlining the successes, challenges and innovations that have arisen through considering the provision of transplant services from a different perspective. We focus particularly on the collaboration with the GDoH, which is unique and may serve as a valuable source of information for others wishing to establish similar partnerships, especially as National Health Insurance comes into effect
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