COVID-19 and globalization

The world is experiencing a major pandemic caused by SARS-CoV-2, the Coronavirus causing COVID-19. This disease first entered the human population in Hubei province, China, in mid-November 2019 and manifested in Wuhan, the largest metropolitan area of Hubei, when a cluster of patients were admitted to hospital with a ‘severe pneumonia of unknown cause’ in early December. Although humanity has survived previous pandemics by infectious agents, the present one is unprecedented in its capacity to take advantage of modern globalization allowing for massive transborder spread at a surprising speed. When writing these lines, the pandemic affects 181 countries and territories, with around 1,084,000 infected subjects, more than 58,000 deaths and 225,000 recovered patients, according to the Johns Hopkins University

Heme and blood-feeding parasites: friends or foes?

Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification

Ozone Response to Aircraft Emissions: Sensitivity Studies with Two-dimensional Models

Our first intercomparison/assessment of the effects of a proposed high-speed civil transport (HSCT) fleet on the stratosphere is presented. These model calculations should be considered more as sensitivity studies, primarily designed to serve the following purposes: (1) to allow for intercomparison of model predictions; (2) to focus on the range of fleet operations and engine specifications giving minimal environmental impact; and (3) to provide the basis for future assessment studies. The basic scenarios were chosen to be as realistic as possible, using the information available on anticipated developments in technology. They are not to be interpreted as a commitment or goal for environmental acceptability

Functional characterisation of Schistosoma japonicum acetylcholinesterase

BACKGROUND: Acetylcholinesterase (AChE) is an important metabolic enzyme of schistosomes present in the musculature and on the surface of the blood stage where it has been implicated in the modulation of glucose scavenging from mammalian host blood. As both a target for the antischistosomal drug metrifonate and as a potential vaccine candidate, AChE has been characterised in the schistosome species Schistosoma mansoni, S. haematobium and S. bovis, but not in S. japonicum. Recently, using a schistosome protein microarray, a predicted S. japonicum acetylcholinesterase precursor was significantly targeted by protective IgG1 immune responses in S. haematobium-exposed individuals that had acquired drug-induced resistance to schistosomiasis after praziquantel treatment. RESULTS: We report the full-length cDNA sequence and describe phylogenetic and molecular structural analysis to facilitate understanding of the biological function of AChE (SjAChE) in S. japonicum. The protein has high sequence identity (88 %) with the AChEs in S. mansoni, S. haematobium and S. bovis and has 25 % sequence similarity with human AChE, suggestive of a highly specialised role for the enzyme in both parasite and host. We immunolocalized SjAChE and demonstrated its presence on the surface of adult worms and schistosomula, as well as its lower expression in parenchymal regions. The relatively abundance of AChE activity (90 %) present on the surface of adult S. japonicum when compared with that reported in other schistosomes suggests SjAChE may be a more effective drug or immunological target against this species. We also demonstrate that the classical inhibitor of AChE, BW285c51, inhibited AChE activity in tegumental extracts of paired worms, single males and single females by 59, 22 and 50 %, respectively, after 24 h incubation with 200 μM BW284c51. CONCLUSIONS: These results build on previous studies in other schistosome species indicating major differences in the enzyme between parasite and mammalian host, and provide further support for the design of an anti-schistosome intervention targeting AChE

Receptor for Fc on the surfaces of schistosomes

Schistosoma mansoni masks its surface with adsorbed host proteins including erythrocyte antigens, immunoglobulins, major histocompatibility complex class I, and beta (2)-microglobulin (beta (2)m), presumably as a means of avoiding host immune responses, How this is accomplished has not been explained. To identify surface receptors for host proteins, we biotinylated the tegument of live S, mansoni adults and mechanically transformed schistosomula and then removed the parasite surface with detergent, Incubation of biotinylated schistosome surface extracts witt l human immunoglobulin G (IgG) Fc-Sepharose resulted in purification of a 97-kDa protein that was subsequently identified as paramyosin (Pmy), using antiserum specific for recombinant Pmy, Fc also bound recombinant S. mansoni Pmy and native S. japonicum Pmy, Antiserum to Pmy decreased the binding of Pmy to Fc-Sepharose, and no proteins bound after removal of Pmy from extracts. Fluoresceinated human Fe bound to the surface, vestigial penetration glands, and nascent oral cavity of mechanically transformed schistosomula, and rabbit anti-Pmy Fab fragments ablated the binding of Fc to the schistosome surface, Pmy coprecipitated with host IgG from parasite surface extracts, indicating that complexes formed on the parasite surface as well as in vitro. Binding of Pmy to Fe was not inhibited by soluble protein A, suggesting that Pmy does not bind to the region between the CH2 and CH3 domains used by many other Fc-binding proteins. beta (2)m did not bind to the schistosome Fc receptor (Pmy), a finding that contradicts reports from earlier workers but did bind to a heteromultimer of labeled schistosomula surface proteins, This is the first report of the molecular identity of a schistosome Fc receptor; moreover it demonstrates an additional aspect of the unusual and multifunctional properties of Pmy from schistosomes and other parasitic flatworms

Increased Iron Stores Correlate with Worse Disease Outcomes in a Mouse Model of Schistosomiasis Infection

Schistosomiasis is a significant parasitic infection creating disease burden throughout many of the world's developing nations. Iron deficiency anemia is also a significant health burden resulting from both nutritional deficit as well as parasitic infection in these countries. In this study we investigated the relationships between the disease outcomes of Schistosoma japonicum infection and iron homeostasis. We aimed to determine if host iron status has an effect on schistosome maturation or egg production, and to investigate the response of iron regulatory genes to chronic schistosomiasis infection. Wild-type C57BL/6 and Transferrin Receptor 2 null mice were infected with S. japonicum, and sacrificed at the onset of chronic disease. Transferrin Receptor 2 null mice are a model of type 3 hereditary hemochromatosis and develop significant iron overload providing increased iron stores at the onset of infection. The infectivity of schistosomes and egg production was assessed along with the subsequent development of granulomas and fibrosis. The response of the iron regulatory gene Hepcidin to infection and the changes in iron status were assessed by real-time PCR and Western blotting. Our results show that Hepcidin levels responded to the changing iron status of the animals, but were not significantly influenced by the inflammatory response. We also show that with increased iron availability at the time of infection there was greater development of fibrosis around granulomas. In conclusion, our studies indicate that chronic inflammation may not be the primary cause of the anemia seen in schistosomiasis, and suggest that increased availability of iron, such as through iron supplementation, may actually lead to increased disease severity

Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target

Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) is considered a lead target for vaccine development against schistosomiasis mansoni because: (1) It is located in the schistosome tegument and is involved in tegument formation; (2) It is strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and (3) It induces high levels of protection against challenge infection in the mouse model. We amplified 211 homologous TSP-2 sequences from male and female S. japonicum worms, which revealed 7 different cDNA subclasses. We expressed in E. coli a region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials. The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development. Further analysis of the distribution of the different subclasses/alleles of the Sj-TSP-2 gene in S. japonicum populations from different endemic areas would be informative

Insights into the Membrane Interactions of the Saposin-Like Proteins Na-SLP-1 and Ac-SLP-1 from Human and Dog Hookworm

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs

Soil-Transmitted Helminths in Tropical Australia and Asia

Soil-transmitted helminths (STH) infect 2 billion people worldwide including significant numbers in South-East Asia (SEA). In Australia, STH are of less concern; however, indigenous communities are endemic for STH, including Strongyloides stercoralis, as well as for serious clinical infections due to other helminths such as Toxocara spp. The zoonotic hookworm Ancylostoma ceylanicum is also present in Australia and SEA, and may contribute to human infections particularly among pet owners. High human immigration rates to Australia from SEA, which is highly endemic for STH Strongyloides and Toxocara, has resulted in a high prevalence of these helminthic infections in immigrant communities, particularly since such individuals are not screened for worm infections upon entry. In this review, we consider the current state of STH infections in Australia and SE