10 resultados para Genome, Viral

em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland


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Matkapuhelimet ovat uusia markkinointikanavia, joiden avulla ihmiset voidaan tavoittaa melkein missä ja milloin vain. Mobiilimarkkinoinnin avulla on mahdollista lähettää henkilökohtaisia mainosviestejä tai tarjota kullekin parhaiten sopivia palveluja. Viraalimarkkinointia voidaan käyttää apuna viestien levittämisessä, aivan kuten internetmainonnassa. Tässä tutkimuksessa on keskitytty matkapuhelimiin lähetettäviin musiikkisuosituksiin sekä siihen miten ihmiset suhtautuvat niihin ja olisivatko he valmiita lähettämään viestejä edelleen kavereilleen. Mobiilimusiikkikysely tehtiin, jotta saataisiin selville asiakkaiden halukkuutta vastaanottaa musiikkisuosituksia matkapuhelimiin, sekä heidän halukkuuttaan viraalimarkkinointia kohtaan. Kyselyyn vastasi kaiken kaikkiaan lähes1300 opiskelijaa. Kyselyn tulokset osoittavat, että lisätutkimusta tulisi tehdä alle 18-vuotiaiden matkapuhelimenkäyttäjien joukossa. Tutkimuksen perusteella löydettiin tekijöitä, jotka vaikuttavat opiskelijoiden halukkuuteen vastaanottaa musiikkisuosituksia matkapuhelimiinsa sekä heidän halukkuuttaan viraalimarkkinointiin.

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Leukemiaa sairastavien lasten kuumeiset infektiot, erityisesti respiratoriset virusinfektiot Tausta: Hengitysteiden virusinfektiot ovat lasten tavallisimpia sairauksia. Infektiota aiheuttava virus voidaan uusilla menetelmillä löytää lähes kaikissa tapauksissa. Leukemiaa sairastavilla lapsilla on perustaudin ja leukemian hoitojen takia tavallista suurempi infektioalttius, ja kuumeilu on tavallista leukemiahoidon aikana. Suurin osa syöpähoidon aikaisten kuumejaksojen syistä jää kuitenkin selvittämättä. Tavoitteet: Prospektiivisen 5 vuotta kestäneen monikeskustutkimuksen tavoitteena oli etsiä uusimmilla mikrobiologisilla menetelmillä leukemiaa sairastavien lasten kuumeen syy. Tätä varten tutkittiin 16 virusta virusviljelyllä, antigeeniosoituksella ja nukleiinihappo-osoituksella. Näytteitä otettiin nenästä, ulosteesta, virtsasta ja verestä. Lisäksi tutkittiin MxA-proteiinin kykyä osoittaa virusinfektio syöpälapsella. Tulokset: Tutkimuksen aikana analysoitiin 138 kuumejaksoa 51 leukemialapsella. Kokonaisseuranta-aika oli 1.5 vuotta/lapsi. Kuumejaksojen ilmaantuvuus oli 2.1 jaksoa potilasta kohden suhteutettuna vuoden riskiaikaan. Hengistysteiden virusinfektio voitiin osoittaa 82 kuumejaksossa (59%). Kaksi tai useampi virus löydettiin 12 %:ssa kuumejaksoista. Tavallisimmat virukset olivat rhinovirus (22 %), respiratory syncytial virus eli RS-virus (11 %), human herpes virus 6 (7 %), human bocavirus (5 %), sytomegalovirus (5 %), parainfluenssavirukset (5 %) ja influenssa A -virus (4 %). Kahdelle potilaalle kehittyi pneumonia, muilla oireet olivat lievät. Veriviljely oli positiivinen 19 kuumejaksossa (14 %), ja puolessa tapauksista löydettiin samanaikaisesti respiratorinen virus. MxA proteini ilmeni veren lymfosyyteissä useimmilla virusinfektioon sairastuneilla syöpälapsilla. Päätelmät: Kuumeiset respiratoriset virusinfektiot ovat tavallisia leukemiaa sairastavilla lapsilla. Infektion oireet ovat tavallisesti vähäiset, mutta pienelle osalle voi kehittyä veriviljelypositiivinen sepsis tai pneumonia. Kuumeen syy jäi selvittämättä vain harvoissa tapauksissa.

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The aim of this study was to investigate herpes simplex virus type 1 (HSV-1)- and measles virus (MV)-induced cell death. HSV-1 with deletion in genes encoding infected cell protein (ICP)4 and protein kinase Us3 (d120) induced apoptosis and cathepsin activation in epithelial (HEp-2) and monocytic (U937) cells. Inhibition of cathepsin activity decreased the amount of d120-induced apoptosis indicating that d120-induced apoptosis could be cathepsin-mediated. Also, HSV-1 infection increased caspase activation suggesting that d120-induced apoptosis is probably caspase-mediated. Cystatin treatment decreased the activity of cathepsins and the replication of HSV-1 indicating that cathepsins contribute to HSV-1 infection. Interestingly, d120 induced also necroptosis in monocytic cells. This is the first report on necroptosis in HSV-1- infected cells. MV induced apoptosis in uninfected bystander T lymphocytes, probably via interaction of MV-infected monocytes with uninfected lymphocytes. The expression of death receptor Fas was clearly increased on the surface of lymphocytes. The number of apoptotic cells and the activation of cathepsins and caspases were increased in MVinfected U937 cells suggesting that MV-induced apoptosis could be cathepsin- and caspase-mediated. Cystatin treatment inhibited cathepsin activities but not MV-induced apoptosis. Besides HSV-1-induced apoptosis, innate immune responses were studied in HSV-1-infection. HSV-1 viruses with either ICP4 and Us3, or Us3 deletion only, increased the expression of Toll-like receptor (TLR)3 and stimulated its downstream pathways leading to increased expression of type I interferon gene and to functional interferons. These findings suggest that besides controlling apoptosis, HSV-1 ICP4 and Us3 genes are involved in the control of TLR3 response in infected cell.

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Gene therapy aims to treat diseases by introducing genetic material to the diseased tissue. For cancer treatment it is important to destroy cancerous cells; this can be achieved by introducing a gene, which induces cell death or by allowing viral vectors to replicate, which also results in destruction of cancerous cells. For cardiac diseases the approach is more like the former, except the gene produces beneficial effects, like angiogenesis. Adenoviruses have many beneficial qualities, which make the virus an interesting gene therapy vector; it can be produced relatively easily, its manipulation is quite easy and it has naturally broad tropism. By removing or replacing certain genes in the adenoviral genome, it can be made non-replicative. In this study, adenoviral receptor expression patterns were characterized in both head and neck squamous cell carcinoma and the human heart. Adenovirus serotype 5 receptor expression in head and neck cancer cell lines was found to be highly variable between cell lines and overall at lower levels, while Ad35 receptor expression was more uniform and at higher levels in all analyzed cell lines. It was also shown that a hybrid virus Ad5/35 is able to infect cells refractory to Ad5, which correlates with receptor expression in these cells. Furthermore, this difference in infection properties extends to cell killing efficiency in case of conditionally replicative viruses. Expression levels of adenoviral receptors CAR, CD46, CD86 and αv-integrins were found to be high both in normal and dilated cardiomyopathy heart tissue. The receptor levels also correlate with transduction efficiency after intracardiac injection. Ad5 showed superior transduction ability compared with Ad5/35, but evoked also a more profound immune reaction when administered this way. Adenoviral gene therapy vectors are the most used delivery vehicles in clinical trials to date. These vectors have proven to be well tolerated and positive results have been obtained when combined with traditional treatments, although poor transduction efficiency has often been reported due to low-level expression of viral receptors on target cells. In spite of this, the results are encouraging and merit for further research.

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In mammals, post-testicular sperm maturation taking place in the epididymis is required for the spermatozoa to acquire the abilities required to fertilize the egg in vivo. The epididymal epithelial cells secrete proteins and other small molecules into the lumen, where they interact with the spermatozoa and enable necessary maturational changes. In this study different in silico, in vitro and in vivo approaches were utilized in order to find novel genes responsible for the function of the epididymis and post-testicular sperm maturation in the mouse. Available online genomic databases were analyzed to identify genes potentially expressed in the epididymis, gene expression profiling was performed by studying their expression in different mouse tissues, and significance of certain genes to fertility was assessed by generating genetically modified mouse models. A recently discovered Pate (prostate and testis expression) gene family was found to be predominantly expressed in the epididymis. It represents one of the largest known gene families expressed in the epididymis, and the members code for proteins potentially involved in defense against microorganisms. Through genetically modified mouse models CRISP4 (cysteine-rich secretory protein 4) was identified to regulate sperm acrosome reaction, and BMYC to inhibit the expression of the Myc proto-oncogene in the developing testis. A mouse line expressing iCre recombinase specifically in the epididymis was also generated. This model can be used to generate conditional, epididymis-specific knock-out models, and will be a valuable tool in fertility studies.

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Plant-virus interactions are very complex in nature and lead to disease and symptom formation by causing various physiological, metabolic and developmental changes in the host plants. These interactions are mainly the outcomes of viral hijacking of host components to complete their infection cycles and of host defensive responses to restrict the viral infections. Viral genomes contain only a small number of genes often encoding for multifunctional proteins, and all are essential in establishing a viral infection. Thus, it is important to understand the specific roles of individual viral genes and their contribution to the viral life cycles. Among the most important viral proteins are the suppressors of RNA silencing (VSRs). These proteins function to suppress host defenses mediated by RNA silencing and can also serve in other functions, e.g. in viral movement, transactivation of host genes, virus replication and protein processing. Thus these proteins are likely to have a significant impact on host physiology and metabolism. In the present study, I have examined the plant-virus interactions and the effects of three different VSRs on host physiology and gene expression levels by microarray analysis of transgenic plants that express these VSR genes. I also studied the gene expression changes related to the expression of the whole genome of Tobacco mosaic virus (TMV) in transgenic tobacco plants. Expression of the VSR genes in the transgenic tobacco plants causes significant changes in the gene expression profiles. HC-Pro gene derived from the Potyvirus Y (PVY) causes alteration of 748 and 332 transcripts, AC2 gene derived from the African cassava mosaic virus (ACMV) causes alteration of 1118 and 251transcripts, and P25 gene derived from the Potyvirus X (PVX) causes alterations of 1355 and 64 transcripts in leaves and flowers, respectively. All three VSRs cause similar up-regulation in defense, hormonally regulated and different stress-related genes and down-regulation in the photosynthesis and starch metabolism related genes. They also induce alterations that are specific to each viral VSR. The phenotype and transcriptome alterations of the HC-Pro expressing transgenic plants are similar to those observed in some Potyvirus-infected plants. The plants show increased protein degradation, which may be due to the HC-Pro cysteine endopeptidase and thioredoxin activities. The AC2-expressing transgenic plants show a similar phenotype and gene expression pattern as HC-Pro-expressing plants, but also alter pathways related to jasmonic acid, ethylene and retrograde signaling. In the P25 expressing transgenic plants, high numbers of genes (total of 1355) were up-regulated in the leaves, compared to a very low number of down-regulated genes (total of 5). Despite of strong induction of the transcripts, only mild growth reduction and no other distinct phenotype was observed in these plants. As an example of whole virus interactions with its host, I also studied gene expression changes caused by Tobacco mosaic virus (TMV) in tobacco host in three different conditions, i.e. in transgenic plants that are first resistant to the virus, and then become susceptible to it and in wild type plants naturally infected with this virus. The microarray analysis revealed up and down-regulation of 1362 and 1422 transcripts in the TMV resistant young transgenic plants, and up and down-regulation of a total of 1150 and 1200 transcripts, respectively, in the older plants, after the resistance break. Natural TMV infections in wild type plants caused up-regulation of 550 transcripts and down-regulation of 480 transcripts. 124 up-regulated and 29 down-regulated transcripts were commonly altered between young and old TMV transgenic plants, and only 6 up-regulated and none of the down-regulated transcripts were commonly altered in all three plants. During the resistant stage, the strong down-regulation in translation-related transcripts (total of 750 genes) was observed. Additionally, transcripts related to the hormones, protein degradation and defense pathways, cell division and stress were distinctly altered. All these alterations may contribute to the TMV resistance in the young transgenic plants, and the resistance may also be related to RNA silencing, despite of the low viral abundance and lack of viral siRNAs or TMV methylation activity in the plants.

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The goal of this thesis is to build a viral marketing management framework for a Finnish medium sized gaming company. This is achieved by first finding and building a theoretical five step management process framework based on literature, analyzing current model and giving recommendations for the case company to develop its own management process. In addition, viral marketing research is still in early stage resulting this study to propose its own take on the definition in the theory part. Empirical part is based on qualitative interviews, campaign material and secondary sources and is aimed to find out and analyze the case company’s current viral marketing state and to give recommendations to it. The final outcome of the study is a general, theoretical management framework for viral marketing campaigns and specified recommendations for the case company.

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Tutkimuksen tavoite on selvittää digitaalisen sisällön ominaisuuksia, jotka vaikuttavat ryhtyvätkö kuluttajat jakamaan, tykkäämään ja kommentoimaan sitä sosiaalisessa mediassa. Tällä pyritään auttamaan yrityksiä ymmärtämään paremmin viraalisuutta, jotta he pystyisivät tuottamaan ja julkaisemaan nettisivuillaan ja sosiaalisessa mediassa parempaa sisältöä, jota kuluttajat jakaisivat enemmän. Tutkimus toteutetaan muodostamalla hypoteeseja mahdollisista ominaisuuksista kirjallisuuden perusteella ja testaamalla niitä regressioanalyyseillä empiirisessä osiossa. Tulokset paljastavat yhdeksän piirrettä, jotka lisäävät viraalisuutta: kiinnostavuus, neutraalisuus, yllättävyys, viihdyttävyys, epäkäytännöllisyys, artikkelin ja Facebook julkaisun pituus, eri sisältö taktiikoiden käyttö (erityisesti blogit ja kuvat lisäävät viraalisuutta) sekä kun mielipidevaikuttaja tai kuuluisuus jakaa sisällön.

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Personalized medicine will revolutionize our capabilities to combat disease. Working toward this goal, a fundamental task is the deciphering of geneticvariants that are predictive of complex diseases. Modern studies, in the formof genome-wide association studies (GWAS) have afforded researchers with the opportunity to reveal new genotype-phenotype relationships through the extensive scanning of genetic variants. These studies typically contain over half a million genetic features for thousands of individuals. Examining this with methods other than univariate statistics is a challenging task requiring advanced algorithms that are scalable to the genome-wide level. In the future, next-generation sequencing studies (NGS) will contain an even larger number of common and rare variants. Machine learning-based feature selection algorithms have been shown to have the ability to effectively create predictive models for various genotype-phenotype relationships. This work explores the problem of selecting genetic variant subsets that are the most predictive of complex disease phenotypes through various feature selection methodologies, including filter, wrapper and embedded algorithms. The examined machine learning algorithms were demonstrated to not only be effective at predicting the disease phenotypes, but also doing so efficiently through the use of computational shortcuts. While much of the work was able to be run on high-end desktops, some work was further extended so that it could be implemented on parallel computers helping to assure that they will also scale to the NGS data sets. Further, these studies analyzed the relationships between various feature selection methods and demonstrated the need for careful testing when selecting an algorithm. It was shown that there is no universally optimal algorithm for variant selection in GWAS, but rather methodologies need to be selected based on the desired outcome, such as the number of features to be included in the prediction model. It was also demonstrated that without proper model validation, for example using nested cross-validation, the models can result in overly-optimistic prediction accuracies and decreased generalization ability. It is through the implementation and application of machine learning methods that one can extract predictive genotype–phenotype relationships and biological insights from genetic data sets.

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Lichens are symbiotic organisms, which consist of the fungal partner and the photosynthetic partner, which can be either an alga or a cyanobacterium. In some lichen species the symbiosis is tripartite, where the relationship includes both an alga and a cyanobacterium alongside the primary symbiont, fungus. The lichen symbiosis is an evolutionarily old adaptation to life on land and many extant fungal species have evolved from lichenised ancestors. Lichens inhabit a wide range of habitats and are capable of living in harsh environments and on nutrient poor substrates, such as bare rocks, often enduring frequent cycles of drying and wetting. Most lichen species are desiccation tolerant, and they can survive long periods of dehydration, but can rapidly resume photosynthesis upon rehydration. The molecular mechanisms behind lichen desiccation tolerance are still largely uncharacterised and little information is available for any lichen species at the genomic or transcriptomic level. The emergence of the high-throughput next generation sequencing (NGS) technologies and the subsequent decrease in the cost of sequencing new genomes and transcriptomes has enabled non-model organism research on the whole genome level. In this doctoral work the transcriptome and genome of the grey reindeer lichen, Cladonia rangiferina, were sequenced, de novo assembled and characterised using NGS and traditional expressed sequence tag (EST) technologies. RNA extraction methods were optimised to improve the yield and quality of RNA extracted from lichen tissue. The effects of rehydration and desiccation on C. rangiferina gene expression on whole transcriptome level were studied and the most differentially expressed genes were identified. The secondary metabolites present in C. rangiferina decreased the quality – integrity, optical characteristics and utility for sensitive molecular biological applications – of the extracted RNA requiring an optimised RNA extraction method for isolating sufficient quantities of high-quality RNA from lichen tissue in a time- and cost-efficient manner. The de novo assembly of the transcriptome of C. rangiferina was used to produce a set of contiguous unigene sequences that were used to investigate the biological functions and pathways active in a hydrated lichen thallus. The de novo assembly of the genome yielded an assembly containing mostly genes derived from the fungal partner. The assembly was of sufficient quality, in size similar to other lichen-forming fungal genomes and included most of the core eukaryotic genes. Differences in gene expression were detected in all studied stages of desiccation and rehydration, but the largest changes occurred during the early stages of rehydration. The most differentially expressed genes did not have any annotations, making them potentially lichen-specific genes, but several genes known to participate in environmental stress tolerance in other organisms were also identified as differentially expressed.