Animal diseases impact on livestock production and threaten food security through loss of animal protein. Additionally, disease impacts may cause major production losses by adding to the cost of livestock production through the necessity to apply costly disease control measures. Taken together, farm animal diseases have been shown to increase poverty levels particularly in poor communities in Africa that have a high dependence on livestock farming for sustenance (Perry et al., 2009). Research to learn more about animal diseases is necessary for the development of appropriate policies and strategies to prevent, control and possibly eradicate costly animal diseases in order to increase socio-economic development and improve livelihood, especially in Africa (Perry et al., 2009). The purpose of this study was to investigate five viruses that cause upper respiratory tract infections in cattle: bovine alphaherpesvirus-1 (BoHV-1), bovine viral diarrhoea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine parainfluenza-3 virus (PI-3) and bovine mastadenovirus-3 (BAV-3), in the rural Mnisi farming community in the Mpumalanga Province, South Africa which is located adjacent to the Kruger National Park (KNP) and private game reserves (Figure 1). The Mnisi Community Project (MCP) is a University of Pretoria initiative that is based on an One Health approach at the human/livestock/wildlife/ecosystem interface. Within the Mnisi community there are a number of dip tanks to which cattle are obligated to attend weekly for FMD inspection. In return, cattle are plunge-dipped free of charge in acaricides, as an aid to control tick-borne diseases such a theileriosis, anaplasmosis, heartwater and redwater. These viruses are known to cause pathology of the respiratory tract and lead to morbidity and even mortality in some cases. In addition, two of the viruses studied here, BoHV-1 and BVDV, can suppress the immune system of the host and also increase the risk of secondary bacterial infections (Valarcher & Hägglund, 2006). This study used a cross sectional design to determine the spatially explicit herd-level antibody seroprevalence of five respiratory tract viruses. A total of 423 sera stored in the Hans Hoheisen Wildlife Centre biobank were collected at 11 dip tanks in the Mnisi communal farming area. A commercially available pentavalent, indirect enzyme linked immunosorbent assay (ELISA) was performed to estimate the seroprevalence of each. The overall proportion of sera that contained antibodies against each pathogen were as follows: 43.3% for BoHV-1; 30.5% for BVDV; 82.5% for BRSV; 44.4% for PI-3 and 83.2% for BAV-3. The prevalence of antibodies against the five respiratory viruses did not appear to be influenced by location, distance from the adjacent wildlife conservation area, time of the year, or sex. However, age was a risk factor as antibodies appeared less frequently in animals less than 12 months of age compared to animals between 12 and 24 months, or older than 24 months. Findings from this study should provide information for the cattle farmers and animal health sector that provide animal health and extension services about the risk of bovine respiratory disease in the Mnisi communal farming area. Appropriate measures to minimize exposure to viral respiratory tract infections are discussed. / Dissertation (MSc)--University of Pretoria, 2018. / Veterinary Tropical Diseases / MSc / Unrestricted

Digitala verktyg i undervisningen har ökat de senaste åren och satsningen 1:1, där varje elev ges tillgång till ett personligt digitalt verktyg, blir allt vanligare. Syftet med denna studie har varit att undersöka vilka möjligheter och svårigheter för kommunikation och samarbete mellan eleverna som ett digitaliserat klassrum kan medföra, samt undersöka hur lärare kan planera och arbeta för att skapa ett samarbetande och kommunicerande klimat i de digitaliserade klassrumsmiljöerna. Utifrån detta syfte formulerades frågeställningarna: Vilka möjligheter och svårigheter för kommunikation och samarbete mellan elever i F-3 kan det digitaliserade klassrummet innebära? Hur kan lärare skapa ett kommunicerande och samarbetande klimat i de digitaliserade klassrummen? Studien är kvalitativ och metoden som har använts för insamling av material är semistrukturerade intervjuer med tre verksamma lärare i F-3. Resultatet visar att den tillgång som 1:1 erbjuder ses som positiv men också att den innebär svårigheter för kommunikationen och samarbetet, och för att ett produktivt samarbete ska äga rum bör eleverna istället arbeta tillsammans på ett verktyg. Resultatet visar också att en tydlig struktur är viktig för att samarbete ska ske, och att detta blir ännu viktigare då digitala verktyg används. Slutligen visar resultatet att lärarna har ett stort ansvar då det kommer till att förmedla dessa strukturer till eleverna, i synnerhet då verktygen används, vilket ställer nya krav på deras planering av undervisning. Min slutsats är att digitala verktyg har möjlighet att bidra till kommunikation och ett produktivt samarbete mellan eleverna, men då behöver lärarna förmedla tydliga strukturer för arbetet.

Human Immunodeficiency Virus 1 (HIV-1) is a lentivirus that forms persistent latently infected reservoirs that are the remaining major hurdle for current HIV-1 treatments. APOBEC3 (A3) proteins are intrinsic retroviral restriction factors that introduce GA mutations during reverse transcription, while Reverse Transcriptase (RT) introduces on average 2-3 mutations every reverse transcription cycle due to a lack of proofreading ability. The goal of this research is to characterize the infectivity and activation of mutated HIV-1 viruses that display reduced transcription upon infection, viruses that we term latency prone viruses (LPVs). We hypothesize that GA transition mutations in the HIV-1 Long Terminal Repeat (LTR) region of the LPVs introduced through Reverse Transcriptase and low levels of A3 protein activity can create HIV-1 sequences that display a reversible, latency-like phenotype. Variable levels of transcription and promoter activation were seen among the LPVs when tested against four classes of Latency Reversing Agents (LRAs). Subsequently, three tested LPVs demonstrated an initial latency-like phenotype before rebounding in infectivity. This project demonstrates for the first time that HIV-1 latency is not simply a byproduct of the infection timing and cellular conditions, but that replication-competent HIV-1 latent viruses can also be created through sublethal mutagenesis of their viral promoter sequence introduced through A3 and RT exposure. The characterization of the complete mechanism of HIV-1 latency induction, maintenance, and reversal is critical in the development of sterilizing and functional cures for HIV-1 infection.

Les facteurs de transcription ETS sont divisés en sous-familles en fonction de leurs similitudes en matière de séquence protéique, de séquences de liaison à l'ADN et d’interactions avec différents cofacteurs. Ils sont régulés par des signaux extracellulaires et contribuent à divers processus cellulaires, dont la prolifération cellulaire et la transformation tumorale. Les gènes de la famille ETS sont fréquemment ciblés par des processus oncogéniques que ce soit des translocations chromosomiques ou des gains du nombre de leurs copies. Le gène PU.1/SPI1 est également ciblé par des mutations ponctuelles inactivatrices dans les hémopathies myéloïdes humaines. Nous avons étudié une mutation somatique récurrente du gène PU.1/SPI1 (c.676C>G, p.Q226E), identifiée chez environ 6% des patients atteints d’une macroglobulinémie de Waldenström (MW), un syndrome lymphoprolifératif B chronique rare. La mutation modifie les caractéristiques de liaison à l'ADN de la protéine mutante, passant des séquences classiques reconnues par SPI1 à des séquences reconnues par d’autres protéines ETS comme ETS1, et d’une liaison à des régions enhancer à une liaison à des régions promotrices. La liaison accrue du mutant de SPI1 aux régions promotrices active des programmes transcriptionnels impliquant des voies de signalisation intracellulaire généralement favorisées par d'autres membres de la famille ETS. Les conséquences fonctionnelles de cette mutation sont une augmentation de la prolifération cellulaire et une diminution de la différenciation lymphoïde B terminale dans une lignée cellulaire modèle et des échantillons primaires de MW. Nous décrivons ici un mécanisme de subversion oncogénique de la fonction d’un facteur de transcription suite à la modification subtile de la spécificité de liaison à l'ADN de la protéine mutante, menant à un arrêt de différenciation. La démonstration qu'une mutation somatique ponctuelle peut modifier l'équilibre de liaison d’un facteur de transcription à l’échelle du génome fournit un paradigme mécanistique sur la façon dont les mutations faux sens dans les gènes codant pour des facteurs de transcription pourraient être oncogéniques dans les tumeurs humaines. / The ETS-domain transcription factors are divided into subfamilies based on protein similarities, DNA binding sequences and interaction with cofactors. They are regulated by extracellular clues and contribute to a variety of cellular processes, including proliferation and transformation. ETS genes are targeted by oncogenic processes through chromosomal translocations and copy number gains. The PU.1/SPI1 gene is also targeted by inactivating point mutations in human myeloid malignancies. We investigated a recurrent somatic missense mutation (Q226E) of the PU.1/SPI1 gene in Waldenström macroglobulinemia, a human B-cell lymphoproliferative disorder. The mutation changes DNA binding of the mutant protein from classical SPI1 to ETS1-like sequences, shifting the balance from binding to promoter regions from enhancers. Increased binding by mutant SPI1 at promoters activates gene expression of intracellular signaling pathways typically promoted by other ETS factor family members. The functional consequences are decreased terminal B-cell differentiation in a model cell line and primary samples. In summary, we describe oncogenic subversion of transcription factor function through subtle alteration DNA binding specificity leading to differentiation arrest. The demonstration that a somatic point mutation subtly changes the balance of genome binding provides a mechanistic paradigm for how missense mutations in transcription factor genes may be oncogenic in human tumors.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19594号 / 医博第4101号 / 新制||医||1014(附属図書館) / 32630 / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 河本 宏, 教授 朝長 啓造 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20992号 / 医博第4338号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小柳 義夫, 教授 髙折 晃史, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bovine Infected Cell Protein 0 (bICP0) is an immediate-early protein encoded by Bovine Herpesvirus-1 that modulates host immune response, activates transcription for all viral promoters, and causes ubiquitin-dependent degradation of proteins. Presented herein is a bICP0 protein-protein interaction (PPI) profile, consisting of 98 cellular and 15 viral proteins, generated through co-immunoprecipitation of bICP0 and its binding partners. The PPI profile was analyzed computationally to identify potential sites of interaction with bICP0 and any cellular pathways that may be influenced by bICP0. Some interactors fall in conjunction with bICP0’s known roles during infection, and others are consistent with known associations of bICP0 homologs. However, some proteins in the PPI profile are involved in apoptosis signaling and mRNA spicing—processes both significant during viral infection and novel to the known functions of bICP0 and its homologs. The interaction and co-localization of some of these proteins with bICP0 was further examined.

Det här arbetet undersöker lärares och skollednings syn på 1:1 på en gymnasieskola i Sverige. 1:1 innebär att varje elev på skolan får tillgång till sin egen personliga dator. Arbetet försöker besvara frågan om hur skolan har påverkats av 1:1.Arbetet är gjort genom kvalitativa intervjuer med lärare och skolledning på skolan. Förutom det har jag använt mig av litteratur och aktuell forskning för att besvara frågeställningarna.Det som har framkommit genom arbetets gång är att det finns ett behov av kompetensutveckling och gemensamma policys kring datoranvändning för att implementeringen av 1:1 ska vara framgångsrik. Det som upplevs som negativt med 1:1 är att eleverna tappar fokus när de får tillgång till en dator. Samtidigt finns det stora möjligheter med att använda datorn i undervisningen, då man får tillgång till fler arbetssätt och kan fånga upp fler elever.

The survey focuses on students from the latter years of primary education in Sweden and their thoughts and attitudes towards their use of internet during class. Over 200 students answered an online-survey with 13 questions about how much, for what, if the use in some way affected them negatively and finally in which ways we should work with internet in education. To analyze the results of the survey the essay uses the theoretical views of cognitivism and constructivism as a basis when concluding what the students think about internet in education, and why they think so. The results of this essay conclude that the students do not generally see the unsanctioned use of computers and smart phones as problematic, but if it is a problem it is to be solved by the teachers, in various manners. Prior research, as well as this paper, find that the results of the already low achievingstudents are the most affected in a negative way. This might create an even bigger dividebetween students but could be diminished by teaching both students and teachers the correct way to use technology and the internet in schools.

A template is a key tool that we use to study knotted periodic orbits in the three-dimensional flow. The simplest type of template is the Lorenz template. In [5], Birman and Williams studied knotted periodic orbits with the aid of the Lorenz template. They discovered remarkable properties of Lorenz knots and links. No half twists exist in the Lorenz template. The new template is referred to be a Lorenz-like template when we add half twists. We looked at the template L(1,-1) in this paper, which has a positive half twist on the left-side and a negative half twist on the right. We look for the different types of knots and links that the template contains. Afterward, it was discovered that some knot types in L(1,-1) are fibered. Additionally, we look into the linking number of links in L(1,-1), as well as L(m; n) for m > 0 and n < 0. We have also explored the subtemplate of L(1,-1).