niryuu/sni-each-converted huggingface dataset:
Background: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition. Methods: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children. Results: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA. Conclusion: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that antimalaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.
Output: Non-Apical Membrane Antigen 1 (AMA1) IgGs from Malian Children Interfere with Functional Activity of AMA1 IgGs as Judged by Growth Inhibition Assay
Background Influenza and other respiratory infections cause excess winter morbidity in children. This study assessed the economic impact of influenza-like illness (ILI) on families with children attending childcare using a societal perspective. Methods We conducted a prospective cohort study in 90 childcare centres and one general practitioner clinic in Sydney, Australia, during 2010. Healthy children aged ≥6 months to <3 years were enrolled. Economic impacts of ILI (temperature ≥37Á8°C or parental report of fever, plus ≥1 respiratory symptoms) were collected at 2 and 4 weeks after ILI onset by telephone interview. Parent-collected respiratory specimens were tested for respiratory viruses using realtime PCR (RT-PCR). Costs associated with healthcare visits, medication usage, carer time lost (work or recreation) and home care and/or additional childcare were collected. Influenza-like illness costs were described and further analysed using a Tobit model. Zero-inflated Poisson regression was employed to compare the numbers of healthcare visits for each ILI. Of 381 children enrolled and analysed, 105 developed 124 ILIs. Specimens were available for 117 ILIs: five were positive by RT-PCR for A(H1N1)pdm09, 39 for adenovirus, 39 for rhinovirus, 15 Please cite this paper as: Yin et al. (2013) Estimates and determinants of economic impacts from influenza-like illnesses caused by respiratory viruses in Australian children attending childcare: a cohort study. Influenza and Other Respiratory Viruses 7(6), 1103-1112.
Output: Estimates and determinants of economic impacts from influenza-like illnesses caused by respiratory viruses in Australian children attending childcare: a cohort study
A 24-year-old African-American man presented with malaise and low back pain and was found to have acute severe rhabdomyolysis followed by acute hemolysis. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was suspected by the presence of blister cells on peripheral smear and was confirmed by a low enzyme activity assay. Our patient reported playing football, along with upper respiratory infection symptoms, prior to presentation. Extensive infectious and toxicology workup was negative; however, several inflammatory proteins were markedly elevated. We hypothesized the large inflammatory burden led to an increased reactive oxygen radical burden that overwhelmed muscle and erythrocyte reducing power. Severe rhabdomyolysis in G6PD deficiency is not a common presentation because skeletal muscles are more resistant to oxidative damage compared to red blood cells. Our case adds to the few existing reports of myolysis in the setting of G6PD deficiency.
Output: New Diagnosis of G6PD Deficiency Presenting as Severe Rhabdomyolysis
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and can cause severe economic loss. Interferon-induced transmembrane (IFITM) proteins constitute a family of viral restriction factors that can inhibit the replication of several types of viruses. Our previous study showed that overexpression of swine IFITM3 (sIFITM3) impeded replication of the FMD virus (FMDV) in BHK-21 cells and mice. In this study, sIFITM3-transgenic (TG) pigs were produced by handmade cloning. Results showed that sIFITM3 was highly overexpressed in many organs of sIFITM3-TG pigs compared to wildtype pigs. After a virulent FMDV strain (O/ES/2001) was intramuscularly inoculated, the sIFITM3-TG pigs showed slightly higher susceptibility to FMDV infection than wild-type pigs. Both groups displayed comparable degrees of clinical symptoms throughout the 14-day observation period. Therefore, the induction of systemic sIFITM3 expression does not protect pigs against FMDV infection. Based on these observations, we propose that a combination of interferons and vaccines be used to control FMDV infections and subsequent FMD outbreaks.
Output: Induction of systemic IFITM3 expression does not effectively control foot-and-mouth disease viral infection in transgenic pigs
Polysaccharide-encapsulated fungi are the chief source of diseases in immunocompromised hosts such as those infected with human immunodeficiency virus or neutropenia patients. Currently available polysaccharide-protein conjugate vaccines are mainly T cell dependent and are usually ineffective in weakened immune systems. In this study, laminarin, a well-characterized ␤-1,3-glucan, was conjugated with a prokaryotically expressed recombinant fragment (amino acids [aa] 39 to 272) of calreticulin (rCRT/39 -272), which exhibits extraordinarily potent immunogenicity and adjuvanticity in experimental animals. The resultant conjugate reserves the immunostimulatory effect of rCRT/39 -272 on naïve murine B cells and is capable of eliciting anti-␤glucan IgG (mostly IgG1) responses in not only BALB/c mice but also athymic nude mice. Laminarin-CRT-induced mouse antibodies (Abs) are able to bind with Candida albicans and inhibit its growth in vitro. In addition, vaccination with laminarin-CRT partially protects mice from lethal C. albicans challenge. These results imply that rCRT/39 -272 could be used as an ideal carrier or adjuvant for carbohydrate vaccines aimed at inducing or boosting IgG responses to fungal infections in immunodeficient hosts.
Output: Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-␤-Glucan IgG Responses in T Cell-Deficient Mice
Infectious disease crises have substantial economic impact. Yet mainstream macroeconomic forecasting rarely takes account of the risk of potential pandemics. This oversight contributes to persistent underestimation of infectious disease risk and consequent underinvestment in preparedness and response to infectious disease crises. One reason why economists fail to include economic vulnerability to infectious disease threats in their assessments is the absence of readily available and digestible input data to inform such analysis. In this Viewpoint we suggest an approach by which the global health community can help to generate such inputs, and a framework to use these inputs to assess the economic vulnerability to infectious disease crises of individual countries and regions. We argue that incorporation of these risks in infl uential macroeconomic analyses such as the reports from the International Monetary Fund's Article IV consultations, rating agencies and risk consultancies would simultaneously improve the quality of economic risk forecasting and reinforce individual government and donor incentives to mitigate infectious disease risks.
Output: Assessment of economic vulnerability to infectious disease crises
Urbanization is a widespread intense land use that generally results in biodiversity decline. Among the taxa capable to adapt to urban landscapes, bats are particularly ubiquitous. Brazil has one of the world's largest diversity of bat species and one of the highest urbanization rates of the world. Yet, few studies have synthesized the biology of bats in urban environments, especially in Brazil. To fill this gap, we systematically reviewed the published scientific literature on the bat fauna found in urban areas of Brazil. The knowledge of urban bats is still incipient and heterogeneously spatially distributed, mostly concentrated in the southeastern region of the country. The assembled list of 84 urban species, of which nineteen are new species records for urban areas (including one new family), represents 47% of the bat richness registered in the country. Thirty-one bat species (37%) were captured exclusively inside forest fragments. Moreover, we provide information on the resources used within the urban matrix by summarizing the roosting sites for 38 bat species, as well as 31 plants consumed by at least twelve bat species. Regarding parasitological aspects, we listed eleven zoonotic parasites hosted by 27 bat species and discussed their potential to become a public health threat. Likewise, we considered the different features linked to urbanization, including impacts on immunity, body condition and susceptibility to acquiring parasites, as possible bat conservation issues. Finally, we defined an agenda for bat studies in urban areas of Brazil.
Output: Bats in urban areas of Brazil: roosts, food resources and parasites in disturbed environments
The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.
Output: Computational Approaches and Challenges to Developing Universal Influenza Vaccines
Efficient antiviral immunity requires interference with virus replication at multiple layers targeting diverse steps in the viral life cycle. We describe here a novel flavivirus inhibition mechanism that results in interferon-mediated obstruction of tick-borne encephalitis virus particle assembly and involves release of malfunctioning membrane-associated capsid (C) particles. This mechanism is controlled by the activity of the interferon-induced protein viperin, a broad-spectrum antiviral interferon-stimulated gene. Through analysis of the viperin-interactome, we identified the Golgi brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) as the cellular protein targeted by viperin. Viperin-induced antiviral activity, as well as C-particle release, was stimulated by GBF1 inhibition and knockdown and reduced by elevated levels of GBF1. Our results suggest that viperin targets flavivirus virulence by inducing the secretion of unproductive noninfectious virus particles via a GBF1-dependent mechanism. This as-yet-undescribed antiviral mechanism allows potential therapeutic intervention.
Output: Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles
Background: Microbial infections have been implicated in initiating and enhancing severity of autoimmune diseases including the demyelinating disease multiple sclerosis (MS). Nevertheless, the incidence of both acute and persisting viral infections without evidence of autoimmune sequelae suggests that this process is well controlled. The conditions promoting or stemming self-reactive (SR) T cells following viral-induced tissue damage thus need to be better defined. Using a non-fatal viral mouse model of encephalomyelitis associated with demyelination and disability, yet ultimate clinical improvement, this study set out to monitor uptake and presentation of endogenous myelin antigens, as well as induction and fate of SR T cells. Methods: Activation and central nervous system (CNS) recruitment of myelin-specific CD4 T cells was analyzed by flow cytometry during encephalomyelitis induced by a glia tropic murine coronavirus. Potential antigen-presenting cells (APC) ingesting myelin were characterized by flow cytometry and their ability to activate SR T cells tested by co-culture with carboxyfluorescein succinimidyl ester (CFSE)-labeled myelin-specific CD4 T cells. Endogenous SR T cell kinetics was analyzed within both cervical lymph nodes and CNS by Enzyme-Linked ImmunoSpot (ELISPOT) following viral infection. The data demonstrate the presence of APC capable of activating SR T cells in both draining lymph nodes and the CNS temporally correlating with overt demyelination. While both the CNS-infiltrating myeloid population and microglia ingested myelin, only CNS-infiltrating APC were capable of presenting endogenous myelin antigen to SR T cells ex vivo. Finally, SR T cell activation from the endogenous T cell repertoire was most notable when infectious virus was controlled and paralleled myelin damage. Although SR T cell accumulation peaked in the persistently infected CNS during maximal demyelination, they were not preferentially retained. Their gradual decline, despite ongoing demyelination, suggested minimal re-stimulation and pathogenic function in vivo consistent with the lack of autoimmune symptoms. The results demonstrate the potential for CNS tissue destruction to induce and recruit SR T cells to the injury site and support a host suppressive mechanism limiting development of autoimmunity.
Output: Self-reactive CD4 + T cells activated during viral-induced demyelination do not prevent clinical recovery
Background: Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reversetranscription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.
Output: BMC Genomics Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE
The complexities of the dynamic processes and their control associated with biological and ecological systems offer many challenges for the control engineer. Over the past decades the application of dynamic modelling and control has aided understanding of their complexities. At the same time using such complex systems as test-beds for new control methods has highlighted their limitations (e.g. in relation to system identification) and has thus acted as a catalyst for methodological advance. This paper continues the theme of exploring opportunities and achievements in applying modelling and control in the bio-and ecological domains. #
Output: Dealing with bio-and ecological complexity: Challenges and opportunities §
A reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) has been described in which a full-length cDNA, corresponding to the IBV (Beaudette-CK) genome, was inserted into the vaccinia virus genome following in vitro assembly of three contiguous cDNAs [Casais, R., Thiel, V., Siddell, S.G., Cavanagh, D., Britton, P., 2001. Reverse genetics system for the avian coronavirus infectious bronchitis virus. J. Virol. 75, 12359-12369]. The method has subsequently been used to generate a recombinant IBV expressing a chimaeric S gene [Casais, R., Dove, B., Cavanagh, D., Britton, P., 2003. Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism. J. Virol. 77, 9084-9089]. Use of vaccinia virus as a vector for the full-length cDNA of the IBV genome has the advantage that modifications can be made to the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. We describe the use of homologous recombination as a method for modifying the Beaudette full-length cDNA, within the vaccinia virus genome, without the requirement for in vitro assembly of the IBV cDNA. To demonstrate the feasibility of the method we exchanged the ectodomain of the Beaudette spike gene for the corresponding region from IBV M41 and generated two recombinant infectious bronchitis viruses (rIBVs) expressing the chimaeric S protein, validating the method as an alternative way for generating rIBVs.
Output: Generation of a recombinant avian coronavirus infectious bronchitis virus using transient dominant selection
Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM.
Output: Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy ScienceDirect
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named ''zymoxins''. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the ''first generation zymoxins'' by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases.
Output: Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin
Canine respiratory coronavirus (CRCoV) is a group II coronavirus that was firstly identified in lung samples of dogs with canine infectious respiratory disease (CIRD) in UK in 2003. We report for the first time the identification of CRCoV in Italy, together with serological evidence that the virus has been circulating in the Italian dog population as from 2005. Serological investigations on 216 dog sera, carried out by an ELISA test using the strictly related bovine coronavirus (BCoV) as antigen, revealed an overall CRCoV seroprevalence of 32.06% in the last 2 years. RT-PCR targeting the S-gene of CRCoV was carried out on 109 lung samples collected from carcasses of dogs submitted for diagnostic investigations. Positive results were obtained from the lungs of a dog of the Apulia region that was co-infected with canine parvovirus type 2. Sequence analysis of the S-gene fragment amplified by RT-PCR (595 bp) showed similarity to group II coronaviruses, with the highest nucleotide identity (98%) to the only CRCoV strain currently available in the GenBank database (strain T101). The results of the present study show that CRCoV is present also in continental Europe, although further studies are required to determine the real pathogenic potential of the virus. #
Output: Serological and molecular evidence that canine respiratory coronavirus is circulating in Italy
The severe acute respiratory syndrome (SARS) coronavirus (CoV) identified in 2003 has infected ∼8000 people worldwide, killing nearly 10% of them. The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). The SARS CoV receptor-binding domain (amino acids N318-T509 of S protein) harbors an extended excursion along its periphery that contacts ACE2 and is designated the receptor-binding motif (RBM, amino acids S432-T486). In addition, the RBM is a major antigenic determinant, able to elicit production of neutralizing antibodies. Hence, the role of the RBM is a bi-functional bioactive surface that can be demonstrated by antibodies such as the neutralizing human anti-SARS monoclonal antibody (mAb) 80R which targets the RBM and competes with the ACE2 receptor for binding. Here, we employ phage-display peptide-libraries to reconstitute a functional RBM. This is achieved by generating a vast collection of candidate RBM peptides that present a diversity of conformations. Screening such 'Conformer Libraries' with corresponding ligands has produced short RBM constructs (ca. 40 amino acids) that can bind both the ACE2 receptor and the neutralizing mAb 80R.
Output: Reconstitution of the receptor-binding motif of the SARS coronavirus
To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at −20 ∘ C. Significant differences in concentrations were found in the median concentration of total protein ( = 0.0336), between 0 months and 1 month ( = 0.0108), 0 and 6 months ( = 0.0023), and 0 and 12 months ( = 0.0027), in mean concentration (g/dL) of albumin ( = 0.0394), between 0 months and 1 month ( = 0.0131), 0 and 6 months ( = 0.0035), and 0 and 12 months ( = 0.0038), and beta-2 fraction ( = 0.0401), between 0 and 6 months ( = 0.0401) and 0 and 12 months ( = 0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at −20 ∘ C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at −20 ∘ C.
Output: Effects of Storage Time on Total Protein and Globulin Concentrations in Bovine Fresh Frozen Plasma Obtained for Transfusion
2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.
Output: Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening
An oligonucleotide array (microarray) incorporating 13,000 elements representing selected strains of hepatitis A virus (HAV), human coxsackieviruses A and B (CVA and CVB), genogroups I and II of Norovirus (NV), and human rotavirus (RV) gene segments 3,4,10, and 11 was designed based on the principle of tiling. Each oligonucleotide was 29 bases long, starting at every 5 th base of every sequence, resulting in an overlap of 24 bases in two consecutive oligonucleotides. The applicability of the array for virus identification was examined using PCR amplified products from multiple HAV and CV strains. PCR products labeled with biotin were hybridized to the array, and the biotin was detected using a brief reaction with Cy3-labeled streptavidin, the array subjected to laser scanning, and the hybridization data plotted as fluorescence intensity against each oligonucleotide in the array. The combined signal intensities of all probes representing a particular strain of virus were calculated and plotted against all virus strains identified on a linear representation of the array. The profile of the total signal intensity identified the strain that is most likely represented in the amplified cDNA target. The results obtained with HAV and CV indicated that the hybridization profile thus generated can be used to identify closely related viral strains. This represents a significant improvement over current methods for virus identification using PCR amplification and amplicon sequencing.
Output: A Microarray Based Approach for the Identification of Common Foodborne Viruses
Public health measures employed to fight against the spread of SARS need to be guided by biomedical knowledge as well as an understanding of the social science aspects of the disease. Using Singapore as a case study, we explore how the state constructs the disease and implements measures targeted at creating a ring of defense around the island and using surveillance to monitor and prevent its spread. While there is support, there is also resentment among some Singaporeans who complain that their right to privacy has been invaded and that over surveillance may have actually occurred. Marginalisation and discrimination have not only affected the local population but in this open economy which is striving to achieve global city status, businesses, tourism, foreign talent, foreign contract workers and foreign students studying in Singapore have also been negatively affected. While Singapore has been applauded by WHO and used as an example of quick and effective response, a holistic approach to the management of infectious disease must address the social implications of strategies that are drawn from medical knowledge alone because it impinges on the social lives of people and how people interact with each other under stressful circumstances.
Output: SARS in Singapore: surveillance strategies in a globalising city
During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For liveattenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wildtype phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. To validate the safety of low-fidelity mutations to increase vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp) were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhibited increased, albeit inconsistent attenuation in an infant mouse model, as well as increased immunogenicity and complete protection against lethal challenge of an adult murine model compared with the parent TC-83. During serial passaging in a highly permissive model, the mutants increased in virulence but remained less virulent than the parent TC-83. These results suggest that the incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines for RNA viruses can confer increased immunogenicity whilst showing some evidence of increased attenuation. However, while in theory such constructs may result in more effective vaccines, the instability of the vaccine phenotype decreases the likelihood of this being an effective vaccine strategy.
Output: Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy
Infectious bursal disease (IBD) continues to pose potential threat to poultry industry all over the world. The disease can spell disaster not only through its infection but also by break of immunity in chickens vaccinated for other diseases. l-Arginine, a ubiquitous, semi-essential amino acid has emerged as an imunostimulant from variety of human and animal studies. In the present study, we demonstrate the stimulatory effects of l-arginine on intestinal intraepithelial lymphocyte (iIELs) functions as well as on systemic immune response in chickens orally vaccinated with live intermediate plus (IP) strain of IBD vaccine. Challenge studies with virulent IBDV revealed complete (100%) protection in IP + l-arginine group compared with 80% protection recorded in IP strain vaccinated chickens. Functional activities of iIELs evaluated by cytotoxicity assay demonstrated significantly high percentage cytotoxicity in IP + l-arginine groups compared with IP group (P < 0.05). Proliferative response of iIELs against IBDV antigen and Con-A was also significantly higher in IP + l-arginine group. Similar results were obtained with peripheral blood mononuclear cell blastogenic response to IBDV and Con-A analyzed as an indicator of systemic cell-mediated immune response. Orally administered IP strain vaccine elicited good antibody titres in both the groups, IP and IP + l-arginine, however, the antibody titres were significantly higher in IP + l-arginine group compared with IP vaccinated group (P < 0.05). These results clearly demonstrate that l-arginine stimulates intestinal and systemic immune response against IBDV.
Output: l-Arginine stimulates intestinal intraepithelial lymphocyte functions and immune response in chickens orally immunized with live intermediate plus strain of infectious bursal disease vaccine
There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.
Output: NOTES Sex-Dependent Differences in Plasma Cytokine Responses to Hantavirus Infection ᰔ
Brown HT was fed to rats of both sexes over three generations at dietary concentrations designed to provide daily intakes of 0, 50, 250 and 500 mg Brown HT/kg body weight/day. During the study a number of females died or failed to nurse their litters. This was so severe following the first mating of F~ adults that the animals were remated to provide the next generation. None of these effects were related to treatment. Body weight and food and water intakes were not adversely affected by treatment. No effects of treatment were seen on reproductive performance or foetal and pup development, apart from slight evidence of a treatment-related retarded ossification of the third sternebrae. Organ weights at autopsy showed two changes, one of which was increased kidney weights which, although not present in every generation, seemed to be related to treatment. The other, increased caecum weights, occurred in adult high-dose females of early generations, but not in males or later generations of the study. Apart from brown coloration of tissues, macroscopic and microscopic examination revealed no treatment-related changes. It was concluded that the no-untoward-effect level in the present study was 250 mg Brown HT/kg/day.
Output: THREE-GENERATION TOXICITY STUDY OF RATS INGESTING BROWN HT IN THE DIET
Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.
Output: MINI REVIEW Rhinovirus Biology, Antigenic Diversity, and Advancements in the Design of a Human Rhinovirus Vaccine
Transcutaneous immunization (TCI) systems that use the skin's immune function are promising needlefree, easy-to-use, and low-invasive vaccination alternative to conventional, injectable vaccination methods. To develop effective TCI systems, it is essential to establish fundamental techniques and technologies that deliver antigenic proteins to antigen-presenting cells in the epidermis and dermis while overcoming the barrier function of the stratum corneum. In this review, we provide an outline of recent trends in the development of techniques for the delivery of antigenic proteins and of the technologies used to enhance TCI systems. We also introduce basic and clinical research involving our TCI systems that incorporate several original devices.
Output: Frontiers of transcutaneous vaccination systems: Novel technologies and devices for vaccine delivery
Since their discovery as a tool for gene transfer, vectors derived from the adeno-associated virus (AAV) have been used for gene therapy applications and attracted scientist to this field for their exceptional properties of efficiency of in vivo gene transfer and the level and duration of transgene expression. For many years, AAVs have been considered as low immunogenic vectors due to their ability to induce long-term expression of non-selfproteins in contrast to what has been observed with other viral vectors, such as adenovirus, for which strong immune responses against the same transgene products were documented. The perceived low immunogenicity likely explains why the use of AAV vectors for vaccination was not seriously considered before the early 2000s. Indeed, while analyses conducted using a variety of transgenes and animal species slowly changed the vision of immunological properties of AAVs, an increasing number of studies were also performed in the field of vaccination. Even if the comparison with other modes of vaccination was not systemically performed, the analyses conducted so far in the field of active immunotherapy strongly suggest that AAVs possess some interesting features to be used as tools to produce an efficient and sustained antibody response. In addition, recent studies also highlighted the potential of AAVs for passive immunotherapy. This review summarizes the main studies conducted to evaluate the potential of AAV vectors for vaccination against infectious agents and discusses their advantages and drawbacks. Altogether, the variety of studies conducted in this field contributes to the understanding of the immunological properties of this versatile virus and to the definition of its possible future applications.
Output: AAV vectors vaccines against infectious diseases
Despite the global zoonotic disease burden, the underlying exposures that drive zoonotic disease emergence are not understood. Here, we aimed to assess exposures to potential sources of zoonotic disease and investigate the demographics, attitudes, and behavior of individuals with sustained occupational animal contact in Vietnam. We recruited 581 animal workers (animal-raising farmers, slaughterers, animal health workers, and rat traders) and their families in southern and central Vietnam into a cohort. Cohort members were followed for 3 years and interviewed annually regarding (1) demography and attitudes regarding zoonotic disease, (2) medical history, (3) specific exposures to potential zoonotic infection sources, and (4) socioeconomic status. Interview information over the 3 years was combined and analyzed as cross-sectional data. Of the 297 cohort members interviewed, the majority (79.8%; 237/297) reported raising livestock; almost all (99.6%; 236/237) reported being routinely exposed to domestic animals, and more than a quarter (28.7%; 68/237) were exposed to exotic animals. Overall, 70% (208/297) reported slaughtering exotic animals; almost all (99.5%; 207/208) reported consuming such animals. The consumption of raw blood and meat was common (24.6%; 73/297 and 37%; 110/297, respectively). Over half (58.6%; 174/297) reported recent occupational animalinduced injuries that caused bleeding; the use of personal protective equipment (PPE) was limited. Our work demonstrates that individuals working with animals in Vietnam are exposed to a wide range of species, and there are limited procedures for reducing potential zoonotic disease exposures. We advocate better education, improved animal security, and enforced legislation of PPE for those with occupational animal exposure in Vietnam.
Output: Occupational Animal Contact in Southern and Central Vietnam
Fibrillarin, one of the major proteins of the nucleolus, plays several essential roles in ribosome biogenesis including pre-rRNA processing and 2 0 -O-ribose methylation of rRNA and snRNAs. Recently, it has been shown that fibrillarin plays a role in virus infections and is associated with viral RNPs. Here, we demonstrate the ability of recombinant fibrillarin 2 from Arabidopsis thaliana (AtFib2) to interact with RNAs of different lengths and types including rRNA, snoRNA, snRNA, siRNA and viral RNAs in vitro. Our data also indicate that AtFib2 possesses two RNA-binding sites in the central (138-179 amino acids) and C-terminal (225-281 amino acids) parts of the protein, respectively. The conserved GCVYAVEF octamer does not bind RNA directly as suggested earlier, but may assist with the proper folding of the central RNA-binding site.
Output: Two RNA-binding sites in plant fibrillarin provide interactions with various RNA substrates
Antibody-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect a short peptide consisting of 20 amino acids. One-binding-site model and two-binding-site model were used for the analysis of the electrical signals, revealing the number of binding sites on an antibody and the dissociation constants between the antibody and the short peptide. In the binding-site models, the surface coverage ratio of the short peptide on the sensor surface is relevant to the electrical signals resulted from the peptideantibody binding on the HEMTs. Two binding sites on an antibody were observed and two dissociation constants, 4.404 Â 10 À 11 M and 1.596 Â 10 À 9 M, were extracted from the binding-site model through the analysis of the surface coverage ratio of the short peptide on the sensor surface. We have also shown that the conventional method to extract the dissociation constant from the linear regression of curve-fitting with Langmuir isotherm equation may lead to an incorrect information if the receptor has more than one binding site for the ligand. The limit of detection (LOD) of the sensor observed in the experimental result ($ 10 pM of the short peptide) is very close to the LOD (around 2.7-3.4 pM) predicted from the value of the smallest dissociation constants. The sensitivity of the sensor is not only dependent on the transistors, but also highly relies on the affinity of the ligand-receptor pair. The results demonstrate that the AlGaN/GaN HEMTs cannot only be used for biosensors, but also for the biological affinity study.
Output: AlGaN/GaN high electron mobility transistors for protein-peptide binding affinity study
Rabies in the greater kudu (Tragelaphus strepsiceros), one of the largest African antelopes, is a phenomenon unique to Namibia. Since the mid-1970s, the country has been plagued by two epizootics that claimed thousands of casualties among the indigenous kudu population. Reasons as to why kudus appear to be exceptionally susceptible to the disease still remain speculative at best. Because the Namibian economy relies heavily on trophy hunting, game meat hunting, and ecotourism, the current severe spread of rabies among kudus calls for effective measures to protect these antelopes. Oral vaccination of kudus may offer a possibility provided efficacious oral rabies vaccines are available. In this screening study, we explored options for attractive baits that facilitate optimal vaccine uptake by the target species and a bait distribution system that maximizes bait availability to the target species meanwhile minimizing bait depletion by non-target species. The results show that gelatin-based baits mixed with local (pods of the camel thorn tree) but also imported (apple-flavored corn meal) attractants are highly attractive for kudus providing a basis for future oral rabies vaccine baits.
Output: Baiting studies on oral vaccination of the greater kudu (Tragelaphus strepsiceros) against rabies