ORCID Profile
0000-0002-5526-6768
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Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.NLM.2006.08.005
Abstract: Learning to perform instrumental tasks is an ability of all animals. In a population of rats, not all in iduals will acquire an operant response for reward. We hypothesized that there could be a genetic explanation for differences between High Consumers (those that acquired the lever press response) and Low Consumers (lever press response is low). Additionally, we proposed that this genetic difference could produce measurable changes in response to novelty. Wistar rats were trained to lever press for a 0.2% saccharin reward and on the 10th day they were placed in a novel open field for 30 min to record locomotor activity. The prefrontal cortex and hippoc us were dissected and qPCR was used to measure mRNA expression. A significant difference (p=.048 2-way ANOVA) in gene expression was observed between Low and High Consumers. A principal component analysis (PCA), to cluster which genes represent this difference, identified 4 genes 5-HT2A and mGlu1 in the hippoc us and AMPA GluR1 and adrenergic alpha2A in the prefrontal cortex. Response to a novel open field also differed since Low Consumers displayed a higher Total Distance in comparison to High Consumers. Additionally, Low Consumers could be sub ided into Low-Lever (with lever press response only when water deprived) and Low-Non-Lever (lever press response is low throughout training). PCA with this sub ision identified an additional nine genes differing within the isions NMDA NR2B and GABAAalpha3 in the prefrontal cortex and adrenergic alpha2B and alpha2A, AMPA GluR1, GluR2 and GluR3, 5-HT1B and GABAAalpha5 in the hippoc us.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.PNPBP.2006.06.010
Abstract: About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly in idualized. In this study, we investigated how in idual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippoc us and amygdala. We found that the long-term alcohol consumption of an in idual could be estimated by the mean of its consumption on Day 2 and 3. This short exposure minimized changes in gene expression induced by alcohol itself. We found a positive correlation in the prefrontal cortex of GABA(A) alpha5 (r=0.96), GABA(B1) (r=0.96), AMPA GluR1 (r=0.93), 5-HT(3A) (r=0.93) and the alpha adrenoceptors (alpha(1A)r=1.00, alpha(1B)r=0.93, alpha(2A)r=0.93) with consumption. In the hippoc us, we found negative correlations with the NMDA NR2A subunit (r=-0.86), the alpha(1A) adrenoceptor (r=-0.89) and the glucocorticoid receptor (r=-0.86). Finally, in the amygdala there was a negative correlation to NMDA NR2A (r= -0.79) and a positive correlation with serotonin 5-HT(2C) (r=0.79). In conclusion, we have used qPCR to identify specific genes in the brain that correlated to alcohol self-administration of an in idual animal. This study suggests that alcohol consumption in the early stages of acquisition depends on the genetic background of the in idual and that the prefrontal cortex is particularly important in this behaviour.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Informa UK Limited
Date: 11-2011
Abstract: Non-coding (nc)RNAs are important players in most biological processes. Although small RNAs such as microRNAs and small interfering RNAs have emerged as exceptionally important regulators of gene expression, great numbers of larger ncRNAs have also been identified. Many of these are abundant and differentially expressed but their functions have in most cases not been elucidated. The social amoeba Dictyostelium discoideum contain the ncRNAs commonly found in eukaryotes. In addition, we previously reported the identification of two novel classes of 42-65 nt long stem-loop forming RNAs, Class I and Class II RNAs, with unknown function. In this study we have further characterized these abundant ncRNAs, which are down regulated during development. We have confirmed expression of 29 Class I RNAs and experimentally verified the formation of the computationally predicted short conserved stem structure. Furthermore, we have for the first time created knockout strains for several small ncRNA genes in D. discoideum and found that deletion of one of the Class I RNAs, DdR-21, results in aberrant development. In addition we have shown that this Class I RNA forms a complex with one or several proteins but do not appear to be associated with ribosomes or polysomes. In a pull down assay, several proteins interacting with DdR-21 were identified, one of these has two RNA recognition motifs (RRMs). The purified RRM containing protein was demonstrated to bind directly and specifically to DdR-21.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BBCAN.2014.03.001
Abstract: Nucleotide sequence modification through single base editing in animals is emerging as an important player in tumorigenesis. RNA editing especially has increased greatly during mammalian evolution and modulates erse cellular functions presumably in a context-dependent manner. Sequence editing impacts development, including pluripotency and hematopoiesis, and multiple recent studies have shown that dysregulation of editing is associated with tumor biology. Much is yet to be learned about the role of sequence editing in human biology but this process is a critical modulator of cell regulation and may present an attractive option for therapeutic intervention in cancer in the future. Sequence editing provides an additional regulatory layer of cancer initiation and progression that may be amenable to therapeutic design. Although editing of both RNA and DNA substrates has been known to occur for some time, the extent and implications of these modifications have been grossly underappreciated until recent genome-wide and disease-association studies were reported. This review highlights the cellular processes controlled by sequence editing, their implications in normal and cancerous states and considers potential targeted therapeutic strategies.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.IJPARA.2010.09.011
Abstract: Giardia intestinalis is one of the major causes of parasite-induced diarrhea. The disease, giardiasis, is caused by trophozoites attaching to the intestinal epithelium, resulting in apoptosis of intestinal epithelial cells, disrupted epithelial barrier function and malabsorption. Microarray studies have detected extensive gene expression changes in intestinal epithelial cells (IECs) during interaction with Giardia trophozoites in vitro. In the present study, we examined this host-parasite interaction further by transcriptional profiling of interacting trophozoites using Giardia microarrays. A total of 200 Giardia transcripts were significantly changed due to the interaction, lasting up to 18 h in complete growth medium. Quantitative reverse transcriptase PCR confirmed the changes in all 12 genes tested using mRNA isolated in separate experiments. Genes encoding proteins previously suggested to be important during host-parasite interactions such as arginine deiminase, enolase and cysteine proteinases were up-regulated early but down-regulated later during the interaction. Cell ision and attachment genes were down-regulated in the late time-points of interaction. The most highly up-regulated genes encode oxygen defense proteins and several members of the high cysteine membrane protein (HCMp) and Gly-rich repeat (GRREAT) families. Putative small RNAs were up-regulated, whereas the 5S rRNA was slightly down-regulated during the interaction with IECs. Thus, there are extensive gene expression changes in Giardia trophozoites and IECs during host-parasite interactions which can be important for establishment of infection and the induction of giardiasis.
Publisher: Springer Berlin Heidelberg
Date: 2013
Publisher: Humana Press
Date: 2013
DOI: 10.1007/978-1-62703-302-2_7
Abstract: High-throughput sequencing methods have become invaluable for detection and analysis of small RNAs. The results are millions of sequences that need to be carefully analyzed by computational methods and preferentially verified by different experimental techniques. Here we describe how to use high-throughput sequencing followed by bioinformatics and northern blot to identify one particular class of small RNA, microRNAs.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.PEPTIDES.2007.09.011
Abstract: Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that in idual alcohol consumption correlates with neurotransmitter gene expression, especially in the prefrontal cortex. To test the hypothesis of Richter, we measured hypothalamic gene expression of receptors or neuropeptides of known relevance for the regulation of food intake using qPCR and correlated this to in idual ethanol consumption in Wistar rats. For validation, gene expression was first correlated with body weight. We found a correlation of dynorphin, somatostatin, melanocortin-4 receptor and serotonin 5-HT(2C) with body weight and trends to correlation for CART, thus confirming the established role of the hypothalamus in the regulation of weight. For ethanol consumption, correlations were found for CRH receptors 1 and 2 and vasopressin while strong trends were observed for galanin receptor 1, orexin receptor 1, MCH and adrenoceptor alpha(1B). Therefore, alcohol consumption does seem to involve several hypothalamic systems which also mediate feeding responses and suggests that the hypothalamus, together with the prefrontal cortex, may determine the 'stopping point' of an in idual.
Publisher: American Society for Microbiology
Date: 06-2006
DOI: 10.1128/EC.00065-06
Abstract: Most eukaryotic mRNAs depend upon precise removal of introns by the spliceosome, a complex of RNAs and proteins. Splicing of pre-mRNA is known to take place in Dictyostelium discoideum , and we previously isolated the U2 spliceosomal RNA experimentally. In this study, we identified the remaining major spliceosomal RNAs in Dictyostelium by a bioinformatical approach. Expression was verified from 17 small nuclear RNA (snRNA) genes. All these genes are preceded by a putative noncoding RNA gene promoter. Immunoprecipitation showed that snRNAs U1, U2, U4, and U5, but not U6, carry the conserved trimethylated 5′ cap structure. A number of ergent U2 species are expressed in Dictyostelium . These RNAs carry the U2 RNA hallmark sequence and structure motifs but have an additional predicted stem-loop structure at the 5′ end. Surprisingly, and in contrast to the other spliceosomal RNAs in this study, the new U2 variants were enriched in the cytoplasm and were developmentally regulated. Furthermore, all of the snRNAs could also be detected as polyadenylated species, and polyadenylated U1 RNA was demonstrated to be located in the cytoplasm.
No related grants have been discovered for Lotta Avesson.