179 research outputs found

    Surface antigens and virulence in Plasmodium falciparum malaria

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    Plasmodium falciparum is an intracellular protozoan that may cause severe forms of malaria. It is a major world health hazard and reaps the highest toll among the children and pregnant mothers of the developing world. An Anopheles mosquito vector injects the pathogen when taking a blood meal. After multiplication in cells of the liver, the parasite escapes and infects red blood cells in a cyclic manner and this is when the clinical manifestations of malaria as a disease become apparent. The parasite causes the infected red blood cells to adhere to each other (rosetting) and to the blood vessel walls (cytoadherence) by exporting highly variable and adhesive PfEMP1 proteins to the erythrocyte surface. Different immunological and genetic properties of the host as well as parasite specific clonal phenotypes determine the outcome of the encounter.We have investigated the parasite side of these events by performing a clinical case-control study where we sampled a score of isolates from patients with severe or mild malaria. These investigations took part in two endemic areas in Uganda; Apac a small rural community in the northern part of the country and Kampala, the capital. The work was partitioned into four different headings where we aimed to explore different aspects of what separates the parasites we found in severe disease patients from the uncomplicated group.Primarily we sought to characterize the sequences of the var genes encoding PfEMP1 expressed in the different patient groups. Through implementing a semi-quantitative PCR amplifying cDNA, massive scale sequencing and a bioinformatics pipeline we we could identify degenerated amino-acid motifs that were either statistically overrepresented in PfEMP1 sequence tags sampled from patients with severe- or mild malaria. These were put in a structural-functional context through 3D modeling and potential sites for receptor interaction were identified. The expression of the var genes in the fresh isolates was further explored in a temporal context to understand the timing of var gene transcription in the patient. We compared semi-and absolutely quantified var genes in a subset of the Ugandan isolates. We chose an approach where we constructed a quantitaive-PCR assay that enumerated the amounts of individual var genes in a heterogeneous solution. The transcription patterns were individual to each isolate and we found that dominance of genes could flux between developmental stages.In a separate study, two of the isolates were chosen to be included in a larger genomics survey of the entire genome by use of a 70-mer oligonucleotide micro-array platform. Size fractionated gDNA from a panel of parasites were hybridized under stringent conditions and cross referenced against the 3D7AH1 genome parasite. The assay could identify a number of gene copy number polymorphisms that were associated to proliferative properties of the parasites, drug resistance or putative invasion related genes. The microarray results were confirmed by PCR and fluorescent in situ DNA hybridization.Finally we studied the growth of fresh in vitro adapted field isolates of children from severe- or mild malaria and found a correlation between the level of rosetting and their multiplication rates. By disrupting rosetting with either anti-immunoglobulin antibodies, heparan sulfate or antibodies to PfEMP1 we could also block the growth of the parasite facilitated by PfEMP1 rosetting. Taken together, these findings argue that P. falciparum specific pheno- and genotypes exist that may predispose for the development of severe malaria. In conclusion, we have found specific molecular evidence for inter-parasite differences in P. falciparum that in the future may be exploited in intervention strategies.List of scientific papersI. Normark J, Nilsson D, Ribacke U, Winter G, Moll K, Wheelock CE, Bayarugaba J, Kironde F, Egwang TG, Chen Q, Andersson B, Wahlgren M (2007). PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 104(40): 15835-40. Epub 2007 Sep 25 https://pubmed.ncbi.nlm.nih.gov/17895392II. Ribacke U, Mok BW, Wirta V, Normark J, Lundeberg J, Kironde F, Egwang TG, Nilsson P, Wahlgren M (2007). Genome wide gene amplifications and deletions in Plasmodium falciparum. Mol Biochem Parasitol. 155(1): 33-44. Epub 2007 May 18 https://pubmed.ncbi.nlm.nih.gov/17599553III. Blomqvist K, Normark J, Nilsson D, Ribacke U, Orikiriza J, Trillkott P, Byarugaba J, Egwang TG, Kironde K, Andersson B, Wahlgren M (2008). Developmental Shift in var gene Transcription in Fresh Plasmodium falciparum isolates. [Manuscript]IV. Ribacke U, Moll K, Normark J, Vogt AM, Chen Q, Flaberg E, Szekely L, Hultenby K, Egwang TG, Wahlgren M (2008). Merozoite invasion in Plasmodium falciparum malaria is facilitated by PfEMP1 mediated rosetting. [Manuscript]</p

    The Chicxulub impact and its different hydrogeological effects on Prehispanic and Colonial settlement in the Yucatan peninsula

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    The Chicxulub impact ~66 million years ago and subsequent geological processes have created different hydrogeological regimes in the Yucatan peninsula, Mexico. These regimes have affected settlement patterns on local and regional scales. This study focuses on the intersection between three of these regimes; the Buried Ejecta within Saline Intrusion Zone, the Albion Formation, and the Ticul Fault Zone. Lake Chichancanab is located in the intersection between these zones. The Prehispanic settlement east of Chichancanab, in the Cochuah region, is distributed evenly whereas the Colonial period settlement of the same area largely stays within the Buried Ejecta within Saline Intrusion Zone. Colonial socioeconomic conditions and the Church limited the Spanish control of the Cochuah region, partially because groundwater access became increasingly more important during the Colonial period

    Blogging about the End Times: Dealing with the Fringes of Archaeology

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    The 2012-phenomenon is based on the idea that something important was expected to occur on December 21, 2012, a date associated with the ancient Maya Long Count calendar. Even though the date has passed, the overall phenomenon is unlikely to disappear because the dominant themes of the end of the world and/or a transformation of consciousness can be found in other ‘alternative’ histories. These non-academic histories are ultimately apocalyptic in nature. The 2012-phenomenon is also an example of an ‘incorporeal hyperobject’, i.e. an object widely distributed and repeated. It is not anchored in a specific time-space unit but it is manifested in many different corporeal objects. The 2012-phenomenon is different from the academic Mayanist incorporeal hyperobject because each of them uses different distinctions of what exists or not. These different objects cannot communicate directly in different media ecologies since different distinctions have formed each one. Hence, there can never be a sincere understanding of each camp. Only by perturbing another object can information be translated into meaning. The blog is such a medium that can affect incorporeal hyperobjects. This article discusses the way one blog has interacted with the 2012-phenomenon

    The making of a home: assembling houses at Nohcacab, Mexico

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    DeLanda's assemblage theory makes it possible to study assemblages like houses, households, organizations and lineages from a flat ontology where materialities and immaterialities are analyzed with the same basic tools. Houses are assemblages consisting of heterogeneous parts that form a functional and expressive whole that is different from its parts. Humans are parts of house assemblages and generate other assemblages extending beyond the physical territory of the buildings themselves. The buildings in the major household assemblage at the small, but densely settled, site of Nohcacab in Quintana Roo, Mexico, are used to show the workings of the multi-scalar assemblage approach. This household consists of smaller parts (artifacts, construction materials and different buildings) and it was part of greater assemblages (community, a nearby causeway system and trade networks).</p

    The coordinative functions of flight strips

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    Cooperation in time-critical and physically distributed worksettings, such as air traffic control, requires extensive coordinationbetween the involved actors. For this coordination to beefficient the controllers rely both on the comprehensive use ofrules and procedures, and on artifacts supporting them infollowing these procedures. At the Copenhagen Air TrafficControl Center this coordination is largely carried out throughthe use of a flight plan database system, paper flight strips, anda closed-circuit television system. In relation to the introductionof a new and increasingly automated system in the year 2003 this paper discusses the coordinative functions served bythese three, soon to be replaced, artifacts from a design perspective.Despite the skepticism expressed in previous research,our results show that a further computerization couldbe successful if the coordinative functions the system currentlyfulfills are properly preserved.</p

    Koloniala och postkoloniala bilder av "mayakulturen"

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