Astrocytes are an attractive cell target for gene therapy but the validation of new therapeutic candidates is needed. We determined whether adeno-associated viral (AAV) vector-mediated overexpression of glutamine synthetase (GS) or excitatory amino acid transporter 2 (EAAT2), or expression of microRNA targeting adenosine kinase (miR-ADK) in hippocampal astrocytes in the rat brain could modulate susceptibility to kainate-induced seizures and neuronal cell loss. Transgene expression was found predominantly in astrocytes following direct injection of glial-targeting AAV9 vectors by 3 weeks post-injection. ADK expression in miR-ADK vector-injected rats was reduced by 94–96% and was associated with a ~50% reduction in the duration of kainate-induced seizures and greater protection of dentate hilar neurons but not CA3 neurons compared to miR-control vector-injected rats. In contrast, infusion of AAV-GS and EAAT2 vectors did not afford any protection against seizures or neuronal damage as the level of transcriptional activity of the glial-fibrillary acidic promoter was too low to drive any significant increase in transgenic GS or EAAT2 relative to the high endogenous levels of these proteins. Our findings support ADK as a prime therapeutic target for gene therapy of temporal lobe epilepsy and suggest alternative approaches including the use of stronger glial promoters are needed to increase transgenic GS and EAAT2 expression to levels that may be required to affect seizure induction and propagation.
SUMMARYThe goal of this work was to identify some of the principles underlying chromatophore growth and development in the European cuttlefish, Sepia officinalis. One set of experiments used a regeneration model to follow the re-growth of black chromatophores for 30 days following excision of a small piece of fin tissue. A separate set of experiments tracked and analyzed the addition of new fin chromatophores during a month of normal, undisturbed growth. We also followed the development of individual chromatophores from their initial appearance to full maturation to determine whether their color type was fixed. Based on the results of these studies, we propose five guiding principles for chromatophore growth and maturation.
We report five cases of Rickettsia australis infection from southern coastal New South Wales, Australia. All patients presented with a cutaneous eruption of erythematous papules and pustules and systemic features of malaise, headache, lymphadenopathy and myalgia. Acute kidney injury (AKI) was present in two of five cases and one of five cases had acute delirium. Improvement was only seen after treatment with doxycycline 100 mg b.i.d. Positive serology for R. australis was present in four of five cases and a positive polymerase chain reaction (PCR) was seen in one of five cases. Histology showed varying features, from neutrophilic vasculitis to Sweet's syndrome and lymphocytic vasculitis. Recent significant advances in the diagnosis of R. australis infection include an eschar swab or biopsy PCR and isolation of specific Rickettsia on serology. These investigations should be considered in the presence of any of the following features: eschar at site of a tick bite or lymphadenopathy and fever with an eruption of erythematous papules and pustules.
Young people's frequency of engagement in reading books for pleasure markedly decreases as they move through the schooling years, reducing their exposure to this beneficial literacy practice. Young people's perceptions of the value of reading can be socially mediated, and positive perception of the value of reading is associated with frequency of engagement in reading. As such, considering how to generate positive social interactions around reading is an important concern when seeking to increase young people's reading frequency. We sought to investigate adolescents' attitudes toward talking about books in order to identify reasons for engagement in discussion about books, as well as factors that constrained engagement in such discussions, with a view to informing best practice for educators seeking to engage adolescents in reading. The findings suggest that adolescents' enjoyment of discussion about books may be related to common interests, enjoyment of discussion to facilitate critical exploration and comprehension, and the possibilities provided for recommendations and access. Adolescents' interests in and ability to engage in book discussions was shaped by mutual text exposure, opportunity, personal preference, disinterested peers and social status maintenance. Findings are considered in relation to classroom practice; the formation of Special Interest Reading Groups within the classroom is considered.
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