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

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

Shepard avocado maturity consumer sensory research

Dry matter content (DM) of avocados represents the amount of carbohydrates and nutrients that have been transported from the tree into the fruit. The longer the avocado remains on the tree, the higher the dry matter, and consequently, %DM is used by growers to decide when avocados are ready to harvest. In the current study, 112 consumers tasted ‘Shepard’, a variety of avocado that can be harvested early in the season. The avocados were collected from a range of locations in Northern Queensland in order to ensure that fruit of varying maturity (%DM) were available for tasting at the same time. Consumers’ liking of flavour increased progressively as the DM content of avocados increased from 18% to 23% but then reached a plateau, where further increases in DM did not result in corresponding increases in liking. The immature (lower DM) avocados were frequently described as having ‘bland/tasteless’ or ‘watery’ flavour as well as being less liked than other avocados. Following tasting, consumers were asked about their experience with avocados and the extent that a quality guarantee offering to refund or replace damaged fruit might increase purchasing. Consumers continued to report a high incidence and severity of damage in the avocados they purchased for consumption at home. The study indicated that consumers’ willingness to buy avocados increased as a consequence of the quality guarantee

Spatial prediction of Plasmodium falciparum prevalence in Somalia

BACKGROUND Maps of malaria distribution are vital for optimal allocation of resources for anti-malarial activities. There is a lack of reliable contemporary malaria maps in endemic countries in sub-Saharan Africa. This problem is particularly acute in low malaria transmission countries such as those located in the horn of Africa. METHODS Data from a national malaria cluster sample survey in 2005 and routine cluster surveys in 2007 were assembled for Somalia. Rapid diagnostic tests were used to examine the presence of Plasmodium falciparum parasites in finger-prick blood samples obtained from individuals across all age-groups. Bayesian geostatistical models, with environmental and survey covariates, were used to predict continuous maps of malaria prevalence across Somalia and to define the uncertainty associated with the predictions. RESULTS For analyses the country was divided into north and south. In the north, the month of survey, distance to water, precipitation and temperature had no significant association with P. falciparum prevalence when spatial correlation was taken into account. In contrast, all the covariates, except distance to water, were significantly associated with parasite prevalence in the south. The inclusion of covariates improved model fit for the south but not for the north. Model precision was highest in the south. The majority of the country had a predicted prevalence of or = 5% prevalence were predominantly in the south. CONCLUSION The maps showed that malaria transmission in Somalia varied from hypo- to meso-endemic. However, even after including the selected covariates in the model, there still remained a considerable amount of unexplained spatial variation in parasite prevalence, indicating effects of other factors not captured in the study. Nonetheless the maps presented here provide the best contemporary information on malaria prevalence in Somalia.AMN is supported by the Wellcome Trust as a Research Training Fellow (#081829). SIH is supported by the Wellcome Trust as Senior Research Fellow (#079091). RWS is supported by the Wellcome Trust as Principal Research Fellow (#079081). AMN, SIH and RWS acknowledge the support of the Kenyan Medical Research Institute

T-cell cytotoxicity in the absence of viral protein synthesis in target cells

CYTOTOXIC T cells lyse only those virus infected target cells in vitro which express, in addition to the viral antigen(s), those K or D region products of the major histocompati-bility complex (MHC) which were present during anti-viral sensitisation in vivo. This 'associative recogniton' by cytotoxic T cells could reflect the interaction of two T-cell receptors with specificity for target K or D gene products and independently for the viral antigen, or one receptor with specificity for virally altered K or D region products (see ref. 1 and refs therein). There are various ways that the MHC antigens could be altered, including 'modification from within', where the virus modifies host protein synthesis by interfering with transcription2, translation or post-translational glycosylation; or 'modification from without' where enzymic or chemical alteration of cell membrane proteins are induced by virus activity at the cell surface. In this report we show that inactivated Sendai virus or isolated Sendai virus envelopes can serve to modify a cell and make it a specific target for Sendai-immune T-cell killing, thus excluding the possibility of 'modification from within' in this system

Access to Artemisinin-Based Anti-Malarial Treatment and its Related Factors in Rural Tanzania.

Artemisinin-based combination treatment (ACT) has been widely adopted as one of the main malaria control strategies. However, its promise to save thousands of lives in sub-Saharan Africa depends on how effective the use of ACT is within the routine health system. The INESS platform evaluated effective coverage of ACT in several African countries. Timely access within 24 hours to an authorized ACT outlet is one of the determinants of effective coverage and was assessed for artemether-lumefantrine (Alu), in two district health systems in rural Tanzania. From October 2009 to June 2011we conducted continuous rolling household surveys in the Kilombero-Ulanga and the Rufiji Health and Demographic Surveillance Sites (HDSS). Surveys were linked to the routine HDSS update rounds. Members of randomly pre-selected households that had experienced a fever episode in the previous two weeks were eligible for a structured interview. Data on individual treatment seeking, access to treatment, timing, source of treatment and household costs per episode were collected. Data are presented on timely access from a total of 2,112 interviews in relation to demographics, seasonality, and socio economic status. In Kilombero-Ulanga, 41.8% (CI: 36.6-45.1) and in Rufiji 36.8% (33.7-40.1) of fever cases had access to an authorized ACT provider within 24 hours of fever onset. In neither of the HDSS site was age, sex, socio-economic status or seasonality of malaria found to be significantly correlated with timely access. Timely access to authorized ACT providers is below 50% despite interventions intended to improve access such as social marketing and accreditation of private dispensing outlets. To improve prompt diagnosis and treatment, access remains a major bottle neck and new more innovative interventions are needed to raise effective coverage of malaria treatment in Tanzania

Risk factors for UK Plasmodium falciparum cases

Background An increasing proportion of malaria cases diagnosed in UK residents with a history of travel to malaria endemic areas are due to Plasmodium falciparum. Methods In order to identify travellers at most risk of acquiring malaria a proportional hazards model was used to estimate the risk of acquiring malaria stratified by purpose of travel and age whilst adjusting for entomological inoculation rate (EIR) and duration of stay in endemic countries. Results Travellers visiting friends and relatives and business travellers were found to have significantly higher hazard of acquiring malaria (adjusted hazard ratio (HR) relative to that of holiday makers 7.4, 95% CI 6.4–8.5, p < 0. 0001 and HR 3.4, 95% CI 2.9-3.8, p < 0. 0001, respectively). All age-groups were at lower risk than children aged 0–15 years. Conclusions These estimates of the increased risk for business travellers and those visiting friends and relatives should be used to inform programmes to improve awareness of the risks of malaria when travelling

Hsp70 in mitochondrial biogenesis

The family of hsp70 (70 kilodalton heat shock protein) molecular chaperones plays an essential and diverse role in cellular physiology, Hsp70 proteins appear to elicit their effects by interacting with polypeptides that present domains which exhibit non-native conformations at distinct stages during their life in the cell. In this paper we review work pertaining to the functions of hsp70 proteins in chaperoning mitochondrial protein biogenesis. Hsp70 proteins function in protein synthesis, protein translocation across mitochondrial membranes, protein folding and finally the delivery of misfolded proteins to proteolytic enzymes in the mitochondrial matrix