4,106 research outputs found
"Plasmodium falciparum" transfection technology for the analysis of "var" gene regulation and knockout investigation
Malaria is an infectious disease caused by protozoans of the genus
Plasmodium, which are injected by the bite of an infected female Anopheles
mosquito during a blood meal. Out of the four species that infect humans, P.
falciparum is the most important. About 40% of the world’s population is at
risk and 500 million cases of malaria occur every year, mainly in sub-
Saharan Africa. Due arising resistance of mosquitoes against insecticides,
the lack of a malaria vaccine, and emerging resistance of parasites against
established drugs, research into new drugs and vaccine targets is most
important.
Morbidity is associated with adherence of infected red blood cells (iRBC) to
endothelial tissue thereby obstructing the blood flow. The major protein
conferring this cytoadherence is the P. falciparum erythrocyte membrane
protein 1 (PfEMP1) anchored in the erythrocyte membrane of infected red
blood cells (iRBCs). PfEMP1 is encoded by the var gene family that consists
of approximately 60 members in the haploid genome of the 3D7 strain. var
genes are expressed mutually exclusive, i.e. only one var gene is expressed
in a parasite at a time and the rest is silenced. In this thesis we were
interested in the regulation of expression and silencing of var genes. For this
purpose we generated transgenic parasite lines that harbored plasmids
expressing luciferase under the control of various fragments of the var gene
upstream region. By comparing luciferase activities in the different lines we
identified the core promoter, two activator-binding sites and a repressorbinding
site. Additionally, we identified a regulatory sequence on the var
upstream region that interacts with the var intron during silencing. Using
quantitative RT-PCR with specific primers for every var gene we were unable
to confirm that the var upstream regions on the transfected plasmids were
recognized by the machinery that ensures mutually exclusive transcription.
In the second part of this thesis, we evaluated phosphodiesterase 1 (PDE1)
as a possible drug target in P. falciparum by creating a knockout parasite
line. PDEs are known drug targets in humans where selective PDE inhibitors
are being used to treat a wide range of diseases. In trypanosomiasis
research PDE inhibitors are promising drug candidates against sleeping
sickness, Nagana or Chagas’ disease. Out of the four PDEs described for P.
falciparum we focused on PfPDE1, which is expressed in blood stage
parasites and in gametocytes and sporozoites. We observed a slightly faster
growth of the knockout parasite line compared to the wildtype indicating that
the knockout parasite had a shorter erythrocytic lifecycle. We found that
PfPDE1 is responsible for 20% of the total cGMP activity observed in late
blood stage parasites and that there is no rescue mechanism of the
remaining PDEs to compensate for the loss of activity. We were not able to
localize PfPDE1 in the parasite. The fact that we could delete PfPDE1 clearly
shows that it is not an essential gene in blood stage forms of P. falciparum
and hence not a good drug target. Nevertheless we created a useful tool to
investigate the role of PfPDE1 in the development of sexual parasite forms
Agent (Capt.) Beck to Commissioner
UteLetter regards a purported \u27antogonism\u27 from White River Utes to the author, Agent Beck. Marisco
The Legacy of Ulrich Beck in Asia: Introduction
This introduction briefly describes the relational trajectory between Ulrich Beck and Asia in the last few years. It draws particular attention to his last words about the role of Asia in the global risk community. Beck began to speak of the concept of metamorphosis in the 2014 Seoul conference as the correct key to understanding emancipatory catastrophism that he had expressed in the 2013 Potsdam conference. He was fascinated by the explanatory power of this concept and was driven to complete a book to explain the cosmopolitan change of the world from this perspective. With his advocacy of cities as cosmopolitan transformers, he urged Asian cities, particularly Seoul, to initiate United Cities of Asia' for a cosmopolitan cooperation for risk governance. Beck also suggested a parliament of risk actors' as a practical task to be realized in the future. In this introduction the author attempts to trace back the formation of these ideas by focusing on the interaction between Beck and Asia before his sudden passing.A&[email protected]
Autoworker and acclaimed author Ben Hamper speaks at the Michigan Writers Series
In an appearance at the Michigan State University Main Library, autoworker and acclaimed author Ben Hamper talks about his career at the General Motors Truck and Bus Plant in Flint, Michigan and reads from various works, including his forward to the book "Working words: punching the clock and kicking out the jams" by M. L. Liebler and from his most famous work, "Rivethead", a cynical and humorous view of life in an auto plant. A question and answer session follows. Hamper is introduced by Michigan State University Professor John P. Beck for the Michigan State University Libraries' Michigan Writers Series
Findings from the LHC/HL-LHC Programme
This note summarizes the results of a social Cost–Benefit Analysis (CBA) of the High Luminosity upgrade of the Large Hadron Collider (HL-LHC). The social CBA methodology is well-suited to assess social costs and benefits of the HL-LHC up to 2038. The analysis shows that the ratio between incremental benefits and incremental costs of the HL-LHC with respect to operating the LHC under normal consolidation (i.e. without high-luminosity upgrade) is slightly over 1.7, meaning that each Swiss Franc invested in the HL-LHC upgrade project pays back approximately 1.7 CHF in societal benefits. The rest of the note is organized as follows. We first discuss the merits of CBA; next, we present the methodology and discuss the results
Henri Temianka Correspondence; (jadwiga beck)
This collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/1133/thumbnail.jp
The relationship between depression and self-mutilation in adolescence
Plan BThe importance of the relationship between depression and self-mutilation in the adolescent population is becoming more apparent. Analysis of these two variables demonstrates that they are correlated with one another in the adolescent population. The present study examines the relationship between depression and self-mutilation. Two scales, the Beck Depression Inventory II (Beck, 1996) and the Self-Harm Survey (Conterio, Lader, & Bloom, 1998) were administered to participants and the scores were correlated to determine whether a relationship existed between the two variables. Participants were residents from a residential treatment center for adolescents. Data analysis using Pearson’s r correlation coefficients were used to determine if there was a positive correlation between depression and self-mutilation. The t-test for independent means was utilized to determine if there was a difference between gender and self-mutilation, age and self-mutilation, as well as length of stay in the residential treatment facility and self-mutilation. The means and standard deviations were also determined for these variables. Statistical differences were indicated based on these findings. Implications of this study as well as recommendations for future studies on depression and self-mutilation were discussed in detail
Exploring the Theory of Metamorphosis: In Dialogue with Ulrich Beck
© The Author(s) 2018. This interview with Ulrich Beck was undertaken in late August 2014. At this juncture Beck was preparing what was to be his final book, The Metamorphosis of the World (2016). The conversation is reflective of Beck's thinking around the theory of metamorphosis at that time and represents his views on the underlying dynamics of social transformation and the mobilizing power of global risks
On the Origins of the Robert Beck Memorial Cinema
In this article, the Author explains the origins of The Robert Beck Memorial Cinema (RBMC), a microcinema located in New York City. The idea was to show movies that no one else could or would
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