Recognition of viral glycoproteins by influenza A-specific cross- reactive cytolytic T lymphocytes

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized

Atmospheric fluctuations below 0.1 Hz during drift-scan solar diameter measurements

Measurements of the power spectrum of the seeing in the range 0.001-1 Hz have been performed in order to understand the criticity of the transits' method for solar diameter monitoring.Comment: 3 pages, 3 figures, proc. of the Fourth French-Chinese meeting on Solar Physics Understanding Solar Activity: Advances and Challenges, 15 - 18 November, 2011 Nice, Franc

Fusion of Sendai virus with the target cell membrane is required for T cell cytotoxicity

INFECTION of mice with viruses can generate cytotoxic T lymphocytes (CTL) which show restricted specificity for target cell lysis. Specific lysis requires that the virus used to prime the target cells must be of the same type as that used to sensitise the CTL, and that both target and CTL cells must express the same major histocompatability complex (MHC) gene product(s). The nature of the viral gene product(s) and their interaction with the MHC gene product(s) have been the subject of recent stud1−5. Previously we used Sendai virus to show that lysable target cells can be obtained using membrane vesicles which contain only the viral glycoproteins, indicating that these may be the specific viral gene products involved in target formation5. Sendai virus contains two glycoproteins—the haemagglutinin-neuraminidase (HANA) which promotes attachment of virus to cells and the fusion protein (F) which is involved in subsequent virus cell fusion7−9. Both activities are necessary for insertion of these viral glycoproteins into the plasma membrane of the cell10. In this letter we suggest that the insertion of the viral glycoproteins into the cell membrane is an essential step in target cell formation since we can show that virus containing an inactive fusion protein precursor (F0) cannot elicit T cell cytotoxicity unless the fusion activity is generated by proteolytic cleavage of the precursor. Sugamura et al. 6 have suggested that it is primarily the F glycoprotein of the Sendai virus envelope which is essential for the formation of the target antigen, as virus lacking the functional activities of F following trypsin digestion was inactive in priming target cells for T cell killing. However, we show that proteolytic inactivation of either of the two glycoproteins (F or HANA) of virus used to prime target cells will abolish the cytotoxic response

Generation of virus-specific cytotoxic T cells in vitro II. Induction requirements with functionally inactivated virus preparations

Using noninfectious Sendai virus preparations after selective enzymatic digestion of either of the two viral envelope glycoproteins, it was possible to study the effect of different virion-cell membrane interactions on virus-specific cytotoxic T lymphocyte (CTL) induction in vitro. Three different virus preparations having capacity for virus- cell fusion, for virus-cell adsorption or lacking the ability to bind to cell membranes, were all active in the generation of virus-specific primary and secondary cytotoxic T cells, when added to the culture. Investigations on the responder cell requirements during CTL induction revealed that activation by addition of virions lacking the capacity to bind to cells was sensitive to the depletion of adherent cells. When virions with fusion and binding capacity were presented on tumor stimulator cells, different requirements with respect to adherent cells were obtained in the primary and secondary CTL response to Sendai virus. The data indicate that different viral antigen-cell membrane interactions govern the activation phase and effector phase of antigen- primed T cell populations, while sensitization of unprimed cells is dependent on the presence of adherent, perhaps antigen-presenting cells

Lead clinical and pre-clinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations

To achieve malarial elimination we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous anti-malarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention; namely impact on case incidence within a vertebrate population (reduction in Ro/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual anti-malarial drugs can impact the number of secondary P.berghei infections over a cycle of transmission. We examine the impact of multiple clinical and pre-clinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6mg/kg) and NITD609 (8.1mg/kg) have significant impact across multiple transmission settings, but artemether/lumefantrine (57/11.8mg/kg), OZ439 (6.5mg/kg) and primaquine (<1.25mg/kg) demonstrated potent efficacy only at lower transmission settings. While directly demonstrating the impact of drug treatment on anti-malarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns

Geographical inequalities in use of improved drinking water supply and sanitation across Sub-Saharan Africa: mapping and spatial analysis of cross-sectional survey data.

BACKGROUND: Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries. METHODS AND FINDINGS: Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991-2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators. CONCLUSIONS: This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda. Please see later in the article for the Editors' Summary

A spatial national health facility database for public health sector planning in Kenya in 2008

BACKGROUND: Efforts to tackle the enormous burden of ill-health in low-income countries are hampered by weak health information infrastructures that do not support appropriate planning and resource allocation. For health information systems to function well, a reliable inventory of health service providers is critical. The spatial referencing of service providers to allow their representation in a geographic information system is vital if the full planning potential of such data is to be realized. METHODS: A disparate series of contemporary lists of health service providers were used to update a public health facility database of Kenya last compiled in 2003. These new lists were derived primarily through the national distribution of antimalarial and antiretroviral commodities since 2006. A combination of methods, including global positioning systems, was used to map service providers. These spatially-referenced data were combined with high-resolution population maps to analyze disparity in geographic access to public health care. FINDINGS: The updated 2008 database contained 5,334 public health facilities (67% ministry of health; 28% mission and nongovernmental organizations; 2% local authorities; and 3% employers and other ministries). This represented an overall increase of 1,862 facilities compared to 2003. Most of the additional facilities belonged to the ministry of health (79%) and the majority were dispensaries (91%). 93% of the health facilities were spatially referenced, 38% using global positioning systems compared to 21% in 2003. 89% of the population was within 5 km Euclidean distance to a public health facility in 2008 compared to 71% in 2003. Over 80% of the population outside 5 km of public health service providers was in the sparsely settled pastoralist areas of the country. CONCLUSION: We have shown that, with concerted effort, a relatively complete inventory of mapped health services is possible with enormous potential for improving planning. Expansion in public health care in Kenya has resulted in significant increases in geographic access although several areas of the country need further improvements. This information is key to future planning and with this paper we have released the digital spatial database in the public domain to assist the Kenyan Government and its partners in the health sector

Treatment-seeking rates in malaria endemic countries

BACKGROUND: The proportion of individuals who seek treatment for fever is an important quantity in understanding access to and use of health systems, as well as for interpreting data on disease incidence from routine surveillance systems. For many malaria endemic countries (MECs), treatment-seeking information is available from national household surveys. The aim of this paper was to assemble sub-national estimates of treatment-seeking behaviours and to predict national treatment-seeking measures for all MECs lacking household survey data. METHODS: Data on treatment seeking for fever were obtained from Demographic and Health Surveys, Malaria Indicator Surveys and Multiple Cluster Indicator Surveys for every MEC and year that data were available. National-level social, economic and health-related variables were gathered from the World Bank as putative covariates of treatment-seeking rates. A generalized additive mixed model (GAMM) was used to estimate treatment-seeking behaviours for countries where survey data were unavailable. Two separate models were developed to predict the proportion of fever cases that would seek treatment at (1) a public health facility or (2) from any kind of treatment provider. RESULTS: Treatment-seeking data were available for 74 MECs and modelled for the remaining 24. GAMMs found that the percentage of pregnant women receiving prenatal care, vaccination rates, education level, government health expenditure, and GDP growth were important predictors for both categories of treatment-seeking outcomes. Treatment-seeking rates, which varied both within and among regions, revealed that public facilities were not always the primary facility type used. CONCLUSIONS: Estimates of treatment-seeking rates show how health services are utilized and help correct reported malaria case numbers to obtain more accurate measures of disease burden. The assembled and modelled data demonstrated that while treatment-seeking rates have overall increased over time, access remains low in some malaria endemic regions and utilization of government services is in some areas limited

Sweetpotato consumer research: insights to increasing consumption

This report provides an evaluation of the behaviours and purchasing drivers of key sweetpotato consumers defined by Nielsen consumer research as Established Couples (two or more adults with no children 17 and under, and head of house 35-59), Senior Couples (two or more adults with no children 17 or under, and head of house 60 or over), and Independent Singles (one person household 35 or over, no children 17 or under). Research was qualitative in nature. Methods used included focus groups, depth interviews and shop-a-longs. The report found that preferences for sweetpotato amongst these groups were varied. In general a smaller torpedo shaped vegetable was valued for ease of preparation and the convenience of being of sufficient size for a meal for two. Satisfaction with sweetpotato was high with negative comments on quality exceedingly rare within discussions. However, shop-a-longs revealed that some quality issues were apparent at retail such as withered product, pitting and occasionally damage. A display with stock resting in any amount of water was a barrier to purchase for consumers and this was apparent on two out 15 occasions. A high quality sweetpotato was of a deep orange/red colour, had a smooth skin and was extremely dense and hard. An inferior sweetpotato was wrinkly, spongy, pitted and damaged. Awareness of sweetpotato was a relatively recent phenomenon amongst the respondents of this study with most recalling eating the vegetable in the last five to 10 years. Life-time eating patterns emerged as a consequence of childhood food experiences such as growing up with a ‘meat and three’ veg philosophy and traditional Australian meals. However, this was dependent on cultural background and those with ties to diverse cultures were more likely to have always known of the vegetable. Sweetpotato trial and consumption coincided with a breaking away from these traditional patterns, or was integrated into conventional meals such as a baked vegetable to accompany roasts. Increased health consciousness also led to awareness of the vegetable. A primary catalyst for consumption within the Established and Senior Couples groups was the health benefits associated with sweetpotato. Consumers had very little knowledge of the specific health properties of the vegetable and were surprised at the number of benefits consumption provided. Sweetpotato was important for diabetics for its low Glycemic Index status. Top-of-the-mind awareness of the vegetable resulted from the onset of the disease. Increasing fibre was a key motive for this demographic and this provided a significant link between consumption and preventing bowel cancer. For those on a weight loss regime, sweetpotato was perceived as a tasty, satisfying food that was low in carbohydrates. Swapping behaviours where white potato was replaced by sweetpotato was often a response to these health concerns. Other health properties mentioned by participants through the course of the research included the precursor β-carotene and Vitamins A & C. The sweetpotato was appreciated for its hedonic and timesaving qualities. For consumers with a high involvement in food, the vegetable was valued for its versatility in meals. These consumers took pride in cooking and the flavour and texture of sweetpotato lent itself to a variety of meals such as soups, salads, roasts, curries, tagines and so on. Participants who had little time or desire to prepare and cook meals valued sweetpotato because it was an easy way to add colour and variety to the plate and because including an orange vegetable to meals is a shortcut to ensuring vitamin intake. Several recommendations are made to the sweetpotato industry. • Vigorously promote the distinct nutritional and health properties of sweetpotatoes, particularly if they can be favourably compared to other vegetables or foods • Promote the salient properties to specific targets such as diabetics, those that are at risk to bowel cancer, and those embarking on a weight-loss regime. Utilise specialist channels of communication such as diabetic magazines and websites • Promote styles of cooking of sweetpotato that would appeal to traditionalists such as roasts and BBQs • Promote the vegetable as a low maintenance vegetable, easy to store, easy to cook and particularly focusing on it as a simple way to boost the appearance and nutritional value of meals. • Promote the vegetable to high food involvement consumers through exotic recipes and linking it to feelings of accomplishment with cooking • Promote the versatility of the vegetable • Devise promotions that link images and tone of communications with enjoying life to the fullest, having time to enjoy family and grandchildren, and of partaking in social activities • Educate retailers on consumer perceptions of quality and ensuring moisture and mould is not present at displays Qualitative information while providing a wealth of detail cannot be extrapolated to the overall target population and this may be considered a limitation to the research. However, within research theory, effective quantitative design is believed to stem from the insights developed from qualitative studies. • Develop and implement a quantitative study on sweetpotato attitudes and behaviours based on the results of this study

Induced currents, frozen charges and the quantum Hall effect breakdown

Puzzling results obtained from torque magnetometry in the quantum Hall effect (QHE) regime are presented, and a theory is proposed for their explanation. Magnetic moment saturation, which is usually attributed to the QHE breakdown, is shown to be related to the charge redistribution across the sample.Comment: 5 pages, 2 figures, Proceedings of the 11th International Symposium "Nanostructures: Physics and Technology", St.Petersburg, Russia, June 23-28, 2003, expanded version with one figure adde