Effects of fatty acids upon LDL catabolism in cultured cells

Imperial Users onl

Preserving Rural Gas Stations: State Financial Assistance for Underground Petroleum Storage Tanks

This Article briefly reviews environmental regulations requiring the upgrading of Underground Storage Tankss, analyzes the development and implementation of the new financial assistance program, and considers the constitutionality of the program in light of state ing of credit prohibitions

Design of a new movement competence assessment for children aged 8–12: A Delphi poll study

Assessing children's movement competence (MC) offers numerous benefits for academics, practitioners, clinicians and children, allowing individuals to meet children's developmental needs and improve their MC. Yet, there is concern that currently available assessment tools only provide a single plane (fundamental movement skills) perspective of a child's MC. The aim of this study was to elicit the expert opinion of a mixture of academics and practitioners from a variety of fields (research, education, sport, physiotherapy, athletic therapy) to design a tool to measure both the fundamental and functional movement skills of children aged 8–12. A three-round Delphi poll with an international panel of 17 academics ( n = 8) and practitioners ( n = 9) was conducted. The consensus was that the assessment should assess (a) object manipulation, (b) locomotor, and (c) stability MC and the assessment layout should be dynamic, incorporating a hybrid model of stations and a circuit. Expert consensus was that most skills were to be performed using the dominant and non-dominant side, with object manipulation skills assessed using process and product criteria. The consensus was also that the assessment should have varied ‘layers’ of marking criteria to cater for varying assessor expertise and have a series of ‘add-on” elements to provide a more detailed evaluation should it be needed. These findings present the foundation and content validity of an assessment which takes a dualistic view of children's movement skills, that could be used across several environments (schools, sports clubs, clinical settings, etc.) and could be suitable for use with a large group of children

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

The aminopeptidase inhibitor CHR-2863 is an orally bioavailable inhibitor of murine malaria

Malaria remains a significant risk in many areas of the world, with resistance to the current antimalarial pharmacopeia an everincreasing problem. The M1 alanine aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) are believed to play a role in the terminal stages of digestion of host hemoglobin and thereby generate a pool of free amino acids that are essential for parasite growth and development. Here, we show that an orally bioavailable aminopeptidase inhibitor, CHR-2863, is efficacious against murine malaria