Filarial Antigens : Targets For Diagnosis, Protection And Pathology

A range of surface, secreted and somatic antigens from filarial parasites have been studies in order to analyse the response of human infected with these pathogens, and to develop reliable diagnostic and prophylactic agents. Diagnostic procedures, which are urgently required for targetting chemotherapy, are being developed by two techniques. Firstly, detection of host antibody is carried out using selected, specific parasite antigens in the form of recombinant peptides from a filarial DNA library. Secondly, measurement of parasite by a monoclonal antibody "antigen-capture" assay. In addition, a longer-term objective of our collaborative study is to isolate molecules which may stimulate the immune system to mount a protective immune response against filarial parasites. A major focus has been a parasite surface glycoprotein known to be closely conserved between adult worms of Brugia malayi, B. timori and Wuchereria bancrofti. This antigen has been cloned from a cDNA library, and its primary sequence established; in addition to being a constant feature of the adult surface, it is expressed by developing larvae and represents an attractive target for vaccine production. Finally, one of the most intriguing questions in filariasis relates to the genesis of pathological reactions. Although this is a difficult problem, we are now beginning to compare the immune responses of individuals of differing clinical status to certain defined parasite antigens, in an attempt to correlate disease development with particular categories of immune response in infected patients. In this way there is hope to advance the basic understanding of filarial disease, while providing practical means for controlling filariasis at the individual and community levels

Comparison of model estimates of the effects of aviation emissions on atmospheric ozone and methane

One of the significant uncertainties in understanding the effects of aviation on climate is the effects of aviation emissions on ozone and atmospheric chemistry. In this study the effects of aviation emissions on atmospheric ozone for 2006 and two projections for 2050 are compared among seven models. The models range in complexity from a two-dimensional coupled model to three-dimensional offline and fully coupled three-dimensional chemistry-climate models. This study is the first step in a critical assessment and comparison among these model results. Changes in tropospheric O3 burdens range from 2.3 Tg-O3/Tg-N to 3.0 Tg-O3/Tg-N, ozone radiative forcings range from 6 to 37 mW/m2, and methane radiative forcings range from -8.3 to -12.5 mW/m2 for the 2006 aviation emissions. As a group, the chemistry transport models tend to have similar responses while the fully coupled models tend to separate from this group and do not show similar responses to each other. ©2013. American Geophysical Union. All Rights Reserved

Planning, implementation, and first results of the Tropical Composition, Cloud and Climate Coupling Experiment (TC4)

The Tropical Composition, Cloud and Climate Coupling Experiment (TC4), was based in Costa Rica and Panama during July and August 2007. The NASA ER-2, DC-8, and WB-57F aircraft flew 26 science flights during TC4. The ER-2 employed 11 instruments as a remote sampling platform and satellite surrogate. The WB-57F used 25 instruments for in situ chemical and microphysical sampling in the tropical tropopause layer (TTL). The DC-8 used 25 instruments to sample boundary layer properties, as well as the radiation, chemistry, and microphysics of the TTL. TC4 also had numerous sonde launches, two ground-based radars, and a ground-based chemical and microphysical sampling site. The major goal of TC4 was to better understand the role that the TTL plays in the Earth's climate and atmospheric chemistry by combining in situ and remotely sensed data from the ground, balloons, and aircraft with data from NASA satellites. Significant progress was made in understanding the microphysical and radiative properties of anvils and thin cirrus. Numerous measurements were made of the humidity and chemistry of the tropical atmosphere from the boundary layer to the lower stratosphere. Insight was also gained into convective transport between the ground and the TTL, and into transport mechanisms across the TTL. New methods were refined and extended to all the NASA aircraft for real-time location relative to meteorological features. The ability to change flight patterns in response to aircraft observations relayed to the ground allowed the three aircraft to target phenomena of interest in an efficient, well-coordinated manner

Excretory-secretory products from adult helminth <i>Nippostrongylus brasiliensis</i> have <i>in vitro</i> bactericidal activity

Introduction. Intestinal helminths and microbiota share the same anatomical niche during infection and are likely to interact either directly or indirectly. Whether intestinal helminths employ bactericidal strategies that influence their microbial environment is not completely understood.Hypothesis. In the present study, the hypothesis that the adult hookworm Nippostrongylus brasiliensis produces molecules that impair bacterial growth in vitro, is tested.Aim. To investigate the in vitro bactericidal activity of Nippostrongylus brasiliensis against commensal and pathogenic bacteria.Methodology. The bactericidal effect of somatic extract and excretory-secretory products of adult Nippostrongylus brasiliensis on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae) bacteria was assessed using growth assays. Minimum inhibitory concentration and minimum bactericidal concentration assays were performed using excretory-secretory products released from the pathogen.Results. Broad-spectrum in vitro bactericidal activity in excretory-secretory products, but not somatic extract of adult Nippostrongylus brasiliensis was detected. The bactericidal activity of excretory-secretory products was concentration-dependent, maintained after heat treatment, and preserved after repeated freezing and thawing.Conclusion. The results of this study demonstrate that helminths such as Nippostrongylus brasiliensis release molecules via their excretory-secretory pathway that have broad-spectrum bactericidal activity. The mechanisms responsible for this bactericidal activity remain to be determined and further studies aimed at isolating and identifying active bactericidal molecules are needed

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

New vs. Given

This squib begins with an argument emphasizing that the grammar of English makes a distinction between constituents that are focused and those that are merely new, hence not given. If the distinction is made via features, we need two features: one indicating focus and one indicating either given or new information. Which one of the two? Semantically, the choice doesn’t matter: whatever information is given is not new and the other way round. For the phonology, there is a difference, however. If the prosody of all-new constituents is default prosody, but the prosody of given constituents is special, we would want to indicate givenness, rather than newness

Surfactant Protein-D is essential for immunity to Helminth Infection

Author Summary Infections by parasitic worms are very common, and controlling them is a major medical and veterinary challenge. Very few drugs exist to treat them, and the parasites can develop resistance to these. In order to find new ways to control worm infections, understanding how our immune system responds to them is essential. Many important parasitic worm infections move through the host lung. In this study we show that a major secreted protein in the lung, Surfactant Protein D (SP-D), is essential for immunity to a parasitic worm infection. We found that this protein binds to worm larvae in the lung to help the immune system kill them. Infecting mice that do not express SP-D with worms demonstrates SP-D is important in this immune response. These mice are unable to launch an effective anti-worm immune response and have many more worms in their intestine compared to mice that do express SP-D. We also show that if we increase SP-D levels in the lung the mouse has better immunity to worms. Together this shows for the first time that SP-D is very important for immunity to worm infections

Modulation of the immune response by nematode secreted acetylcholinesterase revealed by heterologous expression in Trypanosoma musculi

Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host