A Genetically Hard-Wired Metabolic Transcriptome in Plasmodium falciparum Fails to Mount Protective Responses to Lethal Antifolates

Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210) failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS). This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites

Information and Communications Technology industry study:

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Impact assessment study of competition policy and law - the food sector in South Africa

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Which factors influence international research collaboration in Africa?

It is commonly accepted that international research collaboration improves scientists’ abilities and performance. In this chapter, we investigate the question: what are the characteristics of African researchers who collaborate more often with international partners?. Data are taken from Web of Science and a survey that collected detailed information about the individual characteristics of 2954 African researchers in 42 African countries. We use descriptive statistics and an econometric model to discern the characteristics that are associated with higher levels of collaboration with researchers outside Africa. Overall, our results suggest that, on average, researchers who did their doctoral studies outside of Africa, had the opportunity to move abroad (over the past 3 years) and received a higher share of international funding (over the past 3 years), are more likely to collaborate more frequently with researchers outside of Africa. In our conclusions, we discuss that beyond increasing the availability of mobility scholarships and the amount of research funding for African scientists, policymakers and international organisations should also think in incentives to keep long-term research interactions and try to avoid unequal partnerships

Problem-elephant translocation: Translocating the problem and the elephant?

Human-elephant conflict (HEC) threatens the survival of endangered Asian elephants (Elephas maximus). Translocating "problem-elephants" is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: "homers" returned to the capture site, "wanderers" ranged widely, and "settlers" established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals