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miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity
miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity
Development and construction of China
Libraries in China's higher education institutions have been developing in keeping pace with the flourishing development of China's higher education. This article aims to make an introduction to the construction of China's higher education libraries, especially the recent three decades' achievements since China's reform and opening-up in 1978. In this article, the authors draw a general picture of the development of libraries in China's higher education institutions, covering such eight aspects as management, types and positioning, organizational structure and personnel, expenditure and buildings, reader service, building and sharing of resources as well as automation system.</p
Towards the optimal Pixel size of dem for automatic mapping of landslide areas
Determining appropriate spatial resolution of digital elevation model (DEM) is a key step for effective landslide analysis based on remote sensing data. Several studies demonstrated that choosing the finest DEM resolution is not always the best solution. Various DEM resolutions can be applicable for diverse landslide applications. Thus, this study aims to assess the influence of special resolution on automatic landslide mapping. Pixel-based approach using parametric and non-parametric classification methods, namely feed forward neural network (FFNN) and maximum likelihood classification (ML), were applied in this study. Additionally, this allowed to determine the impact of used classification method for selection of DEM resolution. Landslide affected areas were mapped based on four DEMs generated at 1m, 2m, 5m and 10m spatial resolution from airborne laser scanning (ALS) data. The performance of the landslide mapping was then evaluated by applying landslide inventory map and computation of confusion matrix. The results of this study suggests that the finest scale of DEM is not always the best fit, however working at 1m DEM resolution on micro-topography scale, can show different results. The best performance was found at 5m DEM-resolution for FFNN and 1m DEM resolution for results. The best performance was found to be using 5m DEM-resolution for FFNN and 1m DEM resolution for ML classification
Evaluation of the usefulness of a computer‐based learning program to support student learning in pharmacology
This study aims to evaluate the effectiveness of a computer‐based teaching program in supporting and enhancing traditional teaching methods. The program covers the pharmacology of inflammation and has been evaluated with a group of second‐year medical students at a UK university. The study assessed subject‐specific knowledge using a pre‐ and post‐test and surveyed, by questionnaire, students’ perceptions of the usefulness of the program to support learning before and after use. The use of computers for learning amongst this cohort of students was widespread. The results demonstrated an increase in students ‘ knowledge of the pharmacology of inflammation, coupled with a positive attitude towards the CBL program they had used and the advantages that this mode of study may provide in enabling students to manage their own learning. However, students did not feel that the program could substitute for traditional teaching (lectures)
Computability and analysis: the legacy of Alan Turing
We discuss the legacy of Alan Turing and his impact on computability and
analysis.Comment: 49 page
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Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies
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