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1.
PLoS One ; 11(10): e0164548, 2016.
Article in English | MEDLINE | ID: mdl-27760161

ABSTRACT

The transcriptomes of cells infected with lytic and non-lytic variants of coxsackievirus B2 Ohio-1 (CVB2O) were analyzed using next generation sequencing. This approach was selected with the purpose of elucidating the effects of lytic and non-lytic viruses on host cell transcription. Total RNA was extracted from infected cells and sequenced. The resulting reads were subsequently mapped against the human and CVB2O genomes. The amount of intracellular RNA was measured, indicating lower proportions of human RNA in the cells infected with the lytic virus compared to the non-lytic virus after 48 hours. This may be explained by reduced activity of the cellular transcription/translation machinery in lytic enteroviral replication due to activities of the enteroviral proteases 2A and/or 3C. Furthermore, differential expression in the cells infected with the two virus variants was identified and a number of transcripts were singled out as possible answers to the question of how the viruses interact with the host cells, resulting in lytic or non-lytic infections.


Subject(s)
Enterovirus/genetics , Enterovirus/physiology , Gene Expression Profiling , Genetic Variation , Rhabdomyosarcoma/pathology , Cell Line, Tumor , Humans , Intracellular Space/metabolism , Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/virology , Transcription, Genetic
2.
Nature ; 497(7451): 579-84, 2013 May 30.
Article in English | MEDLINE | ID: mdl-23698360

ABSTRACT

Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.


Subject(s)
Evolution, Molecular , Genome, Plant/genetics , Picea/genetics , Conserved Sequence/genetics , DNA Transposable Elements/genetics , Gene Silencing , Genes, Plant/genetics , Genomics , Internet , Introns/genetics , Phenotype , RNA, Untranslated/genetics , Sequence Analysis, DNA , Terminal Repeat Sequences/genetics , Transcription, Genetic/genetics
3.
Cerebellum ; 10(4): 667-82, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21761198

ABSTRACT

Neurons in the cerebellar nuclei (CN) receive inhibitory inputs from Purkinje cells in the cerebellar cortex and provide the major output from the cerebellum, but their computational function is not well understood. It has recently been shown that the spike activity of Purkinje cells is more regular than previously assumed and that this regularity can affect motor behaviour. We use a conductance-based model of a CN neuron to study the effect of the regularity of Purkinje cell spiking on CN neuron activity. We find that increasing the irregularity of Purkinje cell activity accelerates the CN neuron spike rate and that the mechanism of this recoding of input irregularity as output spike rate depends on the number of Purkinje cells converging onto a CN neuron. For high convergence ratios, the irregularity induced spike rate acceleration depends on short-term depression (STD) at the Purkinje cell synapses. At low convergence ratios, or for synchronised Purkinje cell input, the firing rate increase is independent of STD. The transformation of input irregularity into output spike rate occurs in response to artificial input spike trains as well as to spike trains recorded from Purkinje cells in tottering mice, which show highly irregular spiking patterns. Our results suggest that STD may contribute to the accelerated CN spike rate in tottering mice and they raise the possibility that the deficits in motor control in these mutants partly result as a pathological consequence of this natural form of plasticity.


Subject(s)
Action Potentials/physiology , Cerebellar Nuclei/physiology , Computational Biology , Models, Neurological , Neurons/physiology , Animals , Cerebellar Nuclei/cytology , Cerebellar Nuclei/pathology , Computational Biology/methods , Mice , Mice, Neurologic Mutants , Neural Inhibition/physiology , Purkinje Cells/pathology , Purkinje Cells/physiology
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