A Genetic Screen for Attenuated Growth Identifies Genes Crucial for Intraerythrocytic Development of Plasmodium falciparum

A majority of the Plasmodium falciparum genome codes for genes with unknown functions, which presents a major challenge to understanding the parasite's biology. Large-scale functional analysis of the parasite genome is essential to pave the way for novel therapeutic intervention strategies against the disease and yet difficulties in genetic manipulation of this deadly human malaria parasite have been a major hindrance for functional analysis of its genome. Here, we used a forward functional genomic approach to study P. falciparum and identify genes important for optimal parasite development in the disease-causing, intraerythrocytic stages. We analyzed 123 piggyBac insertion mutants of P. falciparum for proliferation efficiency in the intraerythrocytic stages, in vitro. Almost 50% of the analyzed mutants showed significant reduction in proliferation efficiency, with 20% displaying severe defects. Functional categorization of genes in the severely attenuated mutants revealed significant enrichment for RNA binding proteins, suggesting the significance of post-transcriptional gene regulation in parasite development and emphasizing its importance as an antimalarial target. This study demonstrates the feasibility of much needed forward genetics approaches for P. falciparum to better characterize its genome and accelerate drug and vaccine development

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment

A Global Network of Science and Technology Advice in Foreign Ministries

This paper is a product of the International Dialogue on Science and Technology Advice in Foreign Ministries (Vienna Dialogue) in October 2016, involving more than twenty nations and several international organisations. The event was a key step to further develop the Foreign Minister Science and Technology Advisor Network (FMSTAN), growing from an initial group of five nations. The Vienna Dialogue was convened by the Fletcher School of Law and Diplomacy, Tufts University, and the International Institute for Applied Systems Analysis (IIASA) at the Vienna headquarters of IIASA, bringing together diplomats from foreign ministries to consider the value of evidence for informed decision-making by nations with regard to issues, impacts and resources within, across and beyond national boundaries. The evidence comes from the natural and social sciences with engineering and medicine as well as other areas of technology. By building common interests among nations, science is a tool of diplomacy, promoting cooperation and preventing conflict in our world. Science diplomacy was discussed as an international, interdisciplinary and inclusive process to help balance national interests and common interests in view of urgencies today and across generations in our globally-interconnected civilization

Iontophoresis From a Micropipette into a Porous Medium Depends on the ζ-Potential of the Medium

Iontophoresis uses electricity to deliver solutes into living tissue. Often, iontophoretic ejections from micropipettes into brain tissue are confined to millisecond pulses for highly localized delivery, but longer pulses are common. As hippocampal tissue has a ζ-potential of approximately –22 mV, we hypothesized that, in the presence of the electric field resulting from the iontophoretic current, electroosmotic flow in the tissue would carry solutes considerably farther than diffusion alone. A steady state solution to this mass transport problem predicts a spherically symmetrical solute concentration profile with the characteristic distance of the profile depending on the ζ-potential of the medium, the current density at the tip, the tip size and the solute electrophoretic mobility and diffusion coefficient. Of course, the ζ-potential of the tissue is defined by immobilized components of the extracellular matrix as well as cell-surface functional groups. As such, it cannot be changed at will. Therefore, the effect of the ζ-potential of the porous medium on ejections is examined using poly(acrylamide-co-acrylic acid) hydrogels with various magnitudes of ζ-potential, including that similar to hippocampal brain tissue. We demonstrated that nearly neutral fluorescent dextran (3 and 70 kD) solute penetration distance in the hydrogels and OHSCs depends on the magnitude of the applied current, solute properties, and, in the case of the hydrogels, the ζ-potential of the matrix. Steady state solute ejection profiles can be predicted semi-quantitatively

Collaborating with teacher librarians to support adolescents’ literacy and literature learning

The author explores teacher librarians’ ideas about teacher collaborations around literacy and literature learning, roles in collaborations, and the characteristics of good collaborations. Productive and strong collaborations between librarians in schools and their teacher colleagues can enhance students’ learning experiences and outcomes. Semistructured interview data were collected from teacher librarians at 25 schools. The author reports on teacher librarians’ identification of a range of barriers to collaboration in contemporary literacy‐learning contexts and explores the multiple roles that teacher librarians may adopt in collaborative relationships, identifying 11 characteristics of strong collaborations as identified by teacher librarians, which encompass diverse interpersonal qualities and professional activities. Findings offer ideas to enhance the quality of teacher–librarian collaboration, improving literacy outcomes for adolescent students. Not all literacy learning occurs in the typical classroom in school. School libraries can be dynamic spaces in which literacy and literature learning are fostered, because “in schools, libraries are places where text, technology, and literacy converge in concentrated form” (Kapitzke, 2001, p. 451). In this article, I explore teacher librarians’ views on the current state of these collaborations, the kinds of roles that teacher librarians may play, and how teachers and teacher librarians can make collaborative relationships stronger and more effective. My intent is to support high school teachers who wish to work more effectively with their teacher librarians to make the most of learning beyond the classroom