GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites.

BACKGROUND INFORMATION The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. During each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. To date, studies visualizing the apicoplast in live Plasmodium parasites have been restricted to the blood stages of Plasmodium falciparum. RESULTS In the present study, we have generated Plasmodium berghei parasites in which GFP (green fluorescent protein) is targeted to the apicoplast using the specific targeting sequence of ACP (acyl carrier protein), which has allowed us to visualize this organelle in live Plasmodium parasites. During each phase of asexual reproduction, the apicoplast becomes highly branched, but remains as a single organelle until the completion of nuclear division, whereupon it divides and is rapidly segregated into newly forming daughter cells. We have shown that the antimicrobial agents azithromycin, clindamycin and doxycycline block development of the apicoplast during exo-erythrocytic schizogony in vitro, leading to impaired parasite maturation. CONCLUSIONS Using a range of powerful live microscopy techniques, we show for the first time the development of a Plasmodium organelle through the entire life cycle of the parasite. Evidence is provided that interference with the development of the Plasmodium apicoplast results in the failure to produce red-blood-cell-infective merozoites.

The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical active site serine residue instead of a catalytic cysteine. Members of this SERAser subfamily are abundantly expressed in asexual blood stages, rendering them attractive drug and vaccine targets. In this study, we show by antibody localization and in vivo fluorescent tagging with the red fluorescent protein mCherry that the two P. berghei serine-type family members, PbSERA1 and PbSERA2, display differential expression towards the final stages of merozoite formation. Via targeted gene replacement, we generated single and double gene knockouts of the P. berghei SERAser genes. These loss-of-function lines progressed normally through the parasite life cycle, suggesting a specialized, non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed increased expression of the cysteine-type PbSERA3. Compensatory mechanisms between distinct SERA subfamilies may thus explain the absence of phenotypical defect in SERAser disruptants, and challenge the suitability to develop potent antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

Bulletin de la Classe des lettres et des sciences morales et politiques.

Imprint varies.

Canadian Medical Association journal.

English title only, 1911-1958.

The American journal of psychiatry.

Official journal of the American Psychiatric Association.

Risk Criticism : Precautionary Reading in an Age of Environmental Uncertainty /

'Risk Criticism: Reading in an Age of Manufactured Uncertainties' is a study of literary and cultural responses to global environmental risk that offers an environmental humanities approach to understanding risk in an age of unfolding ecological catastrophe. In 2015, the Bulletin of the Atomic Scientists re-set its iconic Doomsday Clock to three minutes to midnight, as close to the apocalypse as it has been since 1953. What pushed its hands was, however, not just the threat of nuclear weapons, but also other global environmental risks that the Bulletin judged to have risen to the scale of the nuclear, including climate change and innovations in the life sciences. If we may once have believed that the end of days would come in a blaze of nuclear firestorm (or the chill of the subsequent nuclear winter), we now suspect that the apocalypse may be much slower, creeping in as chemical toxin, climate change, or bio- or nano- technologies run amok. Taking inspiration from the questions raised by the Bulletin’s synecdochical “nuclear,” 'Risk Criticism' aims to generate a hybrid form of critical practice that brings “nuclear criticism”—a subfield of literary studies that has been, since the Cold War, largely neglected—into conversation with ecocriticism, the more recent approach to environmental texts in literary studies. Through readings of novels, films, theater, poetry, visual art, websites, news reports, and essays, 'Risk Criticism' tracks the diverse ways in which environmental risks are understood and represented today.

Graduate education in biological sciences /

"Report to the Board of Higher Education for its use in developing 'Master Plan--Phase III.'"

New Zealand medical journal.

Journal of the Medical Association of New Zealand.

Critical miscellanies,

I. Robespierre. Carlyle. Byron. Macaulay. Emerson. --II. Vauvenargues. Turgot. Condorcet. Joseph de Maistre. --III. On popular culture. The death of Mr. Mill. Mr. Mill's Autobiography. The life of George Eliot. On Pattison's Memoirs. Harriet Martineau. W.R. Greg; a sketch. France in the eighteenth century. The expansion of England. Auguste Comte.

Critical miscellanies,

Vol. 4, reprinted from the Times and Nineteenth century, has imprint: New York, The Macmillan company, 1908.

Wading through the quagmire: Making sense of dietary supplement utilization

Since the 1980s, numerous studies conducted in the United States have attempted to estimate the prevalence of supplement use among the population (e.g., the National Health and Nutrition Survey and the National Health Interview Surveys). Despite these efforts, the true extent of supplement use is unclear. The literature pertaining to the prevalence of supplement use refers to a confusing array of ambiguous terms. Forming accurate conclusions about supplement use is confounded by differences in terminology and methodology between studies. Direct comparisons between studies are therefore inherently problematic. The emphasis in future investigations should be on standardizing the study design; recording data on daily, weekly, or even monthly use in order to establish the safety and efficacy of supplement use; and adopting a consistent, uniform definition of the term supplement.

Factors Affecting Current and Future Treeline Locations and Dynamics in the Peruvian Andes

The elevational distributions of tropical treelines are thought to be determined by temperature, and are predicted to shift upslope in response to global warming. In contrast to this hypothesis, global-scale studies have shown that only half of all studied treelines are shifting upslope. Understanding how treelines will respond to climate change has important implications for global biodiversity, especially in the tropics, because tropical treelines generally represent the upper-elevation distribution limit of the hyper-diverse cloudforest ecosystem. In Chapter 1, I introduce the idea that grasslands found above tropical treelines may represent a potential grass ceiling which forest species cannot cross or invade. I use an extensive literature review to outline potential mechanisms which may be acting to stabilize treeline and prevent forest expansion into high-elevation grasslands. In Chapters 2-4, I begin to explore these potential mechanisms through the use of observational and experimental methods. In Chapter 2, I show that there are significant numbers of seedlings occurring just outside of the treeline in the open grasslands and that seed rain is unlikely to limit seedling recruitment above treeline. I also show that microclimates outside of the closed-canopy cloudforest are highly variable and that mean temperatures are likely a poor explanation of tropical treeline elevations. In Chapter 3, I show that juvenile trees maintain freezing resistances similar to adults, but nighttime radiative cooling near the ground in the open grassland results in lower cold temperatures relative to the free atmosphere, exposing seedlings of some species growing above treeline to lethal frost events. In Chapter 4, I use a large-scale seedling transplant experiment to test the effects of mean temperature, absolute low temperature and shade on transplanted seedling survival. I find that increasing mean temperature negatively affects seedling survival of two treeline species while benefiting another. In addition, low temperature extremes and the presence of shade also appear to be important factors affecting seedling survival above tropical treelines. This work demonstrates that mean temperature is a poor predictor of tropical treelines and that temperature extremes, especially low temperatures, and non-climatic variables should be included in predictions of current and future tropical treeline dynamics.

How using Technology Enhanced Learning could help modernise traditional large group teaching or Lecturing.

The efficiency of lecturing or large group teaching has been called into question for many years. An abundance of literature details the components of effective teaching which are not provided in the traditional lecture setting, with many alternative methods of teaching recommended. However, with continued constraints on resources large group teaching is here to stay and student’s expect and are familiar with this method.

Technology Enhanced Learning may be the way forward, to prevent educators from “throwing out the baby with the bath water”. TEL could help Educator’s especially in the area of life sciences which is often taught by lectures to engage and involve students in their learning, provide feedback and incorporate the “quality” of small group teaching, case studies and Enquiry Based Learning into the large group setting thus promoting effective and deep learning.

Intergenerational Transfers over the Life Course: Addressing Temporal and Gendered Complexities via a Human Well-being Approach

Research on intergenerational transmissions of poverty and inequality has tended to focus on material transfers. This paper refocuses attention on the intersection of material and psychosocial transfers, which reveals temporal and gendered complexities. It examines three key ideas emerging from the life course literature (relationality, intersectionality and intergenerationality) to shed light on how these complexities might be addressed. It is argued that a human wellbeing lens is potentially useful as a unifying framework to integrate these ideas as it interrogates what living well means over the life course and how it is constructed relationally.