The microneme proteins CTRP and SOAP are not essential for Plasmodium berghei ookinete to oocyst transformation in vitro in a cell free system

<p>Abstract</p> <p>Background</p> <p>Two <it>Plasmodium berghei </it>ookinete micronemal proteins, circumsporozoite and TRAP related protein (CTRP) and secreted ookinete adhesive protein (SOAP) both interact with the basal lamina component laminin. Following gene disruption studies it has been proposed that, apart from their role in motility, these proteins may be required for interactions leading to ookinete-to-oocyst transformation.</p> <p>Methods</p> <p>CTRP and SOAP null mutant <it>P. berghei </it>ookinetes were compared to <it>P. berghei </it>ANKA wild-type for their ability to transform and grow <it>in vitro</it>. To confirm <it>in vitro </it>findings for <it>P</it>. <it>berghei </it>CTRP-KO ookinetes were injected into the haemocoel of <it>An</it>opheles <it>gambiae </it>female mosquitoes.</p> <p>Results</p> <p>Transformation, growth, and viability were comparable for the gene disrupted and wild-type parasites. <it>P</it>. <it>berghei </it>CTRP-KO ookinetes were able to transform into oocysts in the haemocoel of <it>An</it>. <it>gambiae </it>mosquitoes.</p> <p>Conclusion</p> <p>Neither CTRP nor SOAP is required for parasite transformation <it>in vitro</it>. By-passing the midgut lumen allows for the transformation of <it>P</it>. <it>berghei </it>CTRP-KO ookinetes suggesting that it is not required for transformation <it>in vivo</it>.</p

A swarm in July : Beekeeping perspectives on the Old English Wid Ymbe charm

Inscribed in the margins of an eleventh-century manuscript1 of Bede's Ecclesiastical History of the English People and crowded beneath a Latin prayer is a brief bit of advice for beekeepers in the event of a swarm (ymbe), a natural phenomenon in which a substantial portion of an older bee colony migrates en masse with a queen to establish a new colony. The following analysis of this enigmatic text has been inspired largely by three features central to John Miles Foley's vast body of work: interdisciplinarity, collaboration, and comparative research. While the eight lines of alliterative verse that constitute the greater portion of this swarm charm have assured its standing within canonical Old English literature, its insights into traditional apiary practices of Anglo-Saxon England make it equally appropriate subject matter for studies in folklore or even animal science. It is precisely such unlikely intersections that have long served as foci for the transdisciplinary work of John Foley, and it is thus that we now choose it as the subject of analysis for a volume in his honor.2Issue title: Festschrift for John Miles Foley. This article belongs to a special issue of Oral Tradition published in honor of John Miles Foley's 65th birthday and 2011 retirement. The surprise Festschrift, guest-edited by Lori and Scott Garner entirely without his knowledge, celebrates John's tremendous impact on studies in oral tradition through a series of essays contributed by his students from the University of Missouri-Columbia (1979-present) and from NEH Summer Seminars that he has directed (1987-1996). Quotation marks removed to ensure alphabetical order. Title difference as follows; "A Swarm in July" : Beekeeping Perspectives on the Old English Wid Ymbe Char

Isolation of Plasmodium berghei ookinetes in culture using Nycodenz density gradient columns and magnetic isolation

BACKGROUND: Large scale in vitro production of the mosquito stages of malaria parasites remains elusive, with only limited success for complete sporogonic development and only one report of development through to infective sporozoites. The initial step in this process is the production, in vitro, of ookinetes from gametocytaemic blood. Methods for isolation of these ookinetes from blood cells have been described; however, in addition to yield often being low, processing time and potential for contamination by erythrocytes remain high. METHODS: This study compares two procedures for retaining mature ookinetes from blood stage cultures, whilst removing red blood cells and other contaminants prior to further culture of the parasite. The well established method of isolation on Nycodenz cushions is compared with a novel method utilizing the innate magnetic properties of the haem pigment crystals found in the cytoplasm of ookinetes. RESULTS: Yield and viability of ookinetes were similar with both isolation methods. However, in our hands magnetic isolation produced a cleaner ookinete preparation much more quickly. Moreover, decreasing the flow rate through the magnetic column could further enhance the yield. CONCLUSION: We recommend the enrichment of an ookinete preparation prior to further culture being performed using the magnetic properties of Plasmodium berghei ookinetes as an alternative to their density. The former technique is faster, removes more erythrocytes, but day-to-day costs are greater

Comparing the Mental Health of Healthcare Students: Mental Health Shame and Self-compassion in Counselling, Occupational Therapy, Nursing and Social Work Students

Poor mental health of healthcare students is a cause for concern in many universities. Though previous research has identified mental health shame and self-compassion as critical in this student group, how these variables differ across different healthcare disciplines remains to be evaluated. Healthcare students (n = 344; counselling, occupational therapy, social work and nursing) completed measures regarding these variables. MANOVA and regression analyses were performed. (1) Counselling and nursing students were more depressed than occupational therapy students; (2) nursing students were more anxious than occupational therapy and social work students; (3) occupational therapy students had more positive attitudes towards mental health than the others; and (4) nursing students worried about their own reputation associated with their family more than counselling students. Self-compassion was the strongest predictor of mental health in all groups; however, the effect sizes varied: largest in nursing and smallest in social work students. Findings will help inform effective interventions for students in each healthcare discipline

Feminist geographies in Aotearoa New Zealand: cultural, social and political moments

Aotearoa New Zealand is a nation of promise, potential and enigma: it was the first country in the world where women gained the vote in 1893 and now boasts the youngest woman world leader in 2017. It is also a postcolonial nation where structural racism, homophobia, and sexism persist, yet it has also given legal personhood to a river. Our Country Report foregrounds Aotearoa New Zealand feminist geographic scholarship that responds to, reflects, and sometimes resists such contrasts and contradictions at the national scale. We employ the lens of the 2017 national election to critically engage with current gendered and indigenous politics in the country. Analyzing these politics through three ‘feminist moments,’ our paper highlights the breadth and scope of current Aotearoa New Zealand feminist geographic scholarship and directions

Site-Specific Integration and Expression of an Anti-Malarial Gene in Transgenic Anopheles gambiae Significantly Reduces Plasmodium Infections

Diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. Historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. To circumvent these limitations the Streptomyces phage phiC31 integrase system has been successfully adapted for site-specific transgene integration in insects. Here, we present the first site-specific transformation of Anopheles gambiae, the principal vector of human malaria. Mosquitoes were initially engineered to incorporate the phiC31 targeting site at a defined genomic location. A second phase of genetic modification then achieved site-specific integration of Vida3, a synthetic anti-malarial gene. Expression of Vida3, specifically in the midgut of bloodfed females, offered consistent and significant protection against Plasmodium yoelii nigeriensis, reducing average parasite intensity by 85%. Similar protection was observed against Plasmodium falciparum in some experiments, although protection was inconsistent. In the fight against malaria, it is imperative to establish a broad repertoire of both anti-malarial effector genes and tissue-specific promoters for their expression, enabling those offering maximum effect with minimum fitness cost to be identified. In the future, this technology will allow effective comparisons and informed choices to be made, potentially leading to complete transmission blockade

Growing our future: Introducing the Pacific School Food Network to support healthy school food and nutrition environments for better nourished children in the Pacific Islands

Food systems in the Pacific Islands (P.I.) are transitioning from local, traditional diets to those with low fruit and vegetable intake and largely based on ultra-processed foods that are often, but not always, imported. Alongside changes in diet and health outcomes, there is a loss of traditional and sociocultural dimensions of food, resulting in poor quality diets in many P.I. populations, including children. Besides high rates of overweight and obesity, in some areas stunting rates are up to 48.4%,1 and prevalence of anaemia (5-14 years) as high as 45%.2 After many years of limited multisectoral action and effort to enact sustainable change across policy and practice, there is growing interest in improving school food and nutrition environments (SFE) in the region. Against this backdrop of limited capacity, coordination, effort, research and evidence, the Pacific School Food Network (PSFN) was formed

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD) : effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences

Characterisation of Innate Fungal Recognition in the Lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung