niryuu/sni-each-converted huggingface dataset:
The resurgence of severe acute respiratory syndrome (SARS) is still a threat because the causative agent remaining in animal reservoirs is not fully understood, and sporadic cases continue to be reported. Developing high titers of anti-SARS hyperimmune globulin to provide an alternative pathway for emergent future prevention and treatment of SARS. Methods: SARS coronavirus (CoV)F69 (AY313906) and Z2-Y3 (AY394989) were isolated and identified from 2 different Cantonese onset SARS patients. Immunogen was prepared from SARS-CoV F69 strain. Six health horses were immunized 4 times and serum was collected periodically to measure the profile of specific IgG and neutralizing antibodies using indirect enzyme-linked immunosorbent assay and a microneutralization test. Sera were collected in large amounts at the peak, where IgG was precipitated using ammonium sulphate and subsequently digested with pepsin. The product was then purified using anion-exchange chromatography to obtain F(ab') 2 fragments. Results: The specific IgG and neutralizing antibody titers peaked at approximately week 7 after the first immunization, with a maximum value of 1:14210. The sera collected at the peak were then purified. Fragment of approximately 15 g F(ab') 2 was obtained from 1 litre antiserum and the purity was above 90% with the titer of 1:5120, which could neutralize the other strain (SARS-CoV Z2-Y3) as well. Conclusion: This research provides a viable strategy for the prevention and treatment of SARS coronavirus infection with equine hyperimmune globulin, with the purpose of combating any resurgence of SARS.
Output: Preparation and development of equine hyperimmune globulin F(ab') 2 against severe acute respiratory syndrome coronavirus 1
Respiratory immunization is an attractive way to generate systemic and mucosal protective memory responses that are required for preventing mucosally transmitted infections. However, the molecular and cellular mechanisms for controlling memory T cell responses remain incompletely understood. In this study, we investigated the role of respiratory macrophage (MU) in regulating CD4 T cell responses to recombinant adenovirus-based (rAd) vaccines. We demonstrated that rAd intranasal (i.n.) vaccination induced migration and accumulation of respiratory MU and circulatory monocytes in the mediastinal lymph nodes and lung parenchyma. Under the influence of respiratory MU CD4 T cells exhibited slow proliferation kinetics and an increased tendency of generating central memory, as opposed to effector memory, CD4 T cell responses in vitro and in vivo. Correspondingly, depletion of MU using clodronatecontaining liposome prior to i.n. immunization significantly enhanced CD4 T cell proliferation and increased the frequency of CD4 memory T cells in the airway lumen, demonstrating that MU initially serve as a negative regulator in limiting generation of mucosal tissue-resident memory CD4 T cells. However, clodronate-containing liposome delivery following i.n. immunization markedly reduced the frequencies of memory CD4 T cells in the airway lumen and spleen, indicating that respiratory MU and potentially circulating monocytes are critically required for maintaining long-term memory CD4 T cells. Collectively, our data demonstrate that rAd-induced mucosal CD4 T memory responses are regulated by respiratory MU and/or monocytes at multiple stages.
Output: Respiratory macrophages regulate CD4 T memory responses to mucosal immunization with recombinant adenovirus-based vaccines
Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.
Output: In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection
Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies. In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria. Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes. Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic. Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage. Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300-1800 input genome copies. LODs increased 10-fold in the presence of contaminating human genome DNA. In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer. Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.
Output: Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes OPEN
The biological function of bovine colostral immunoglobulins is to provide the newborn calf with adequate passive immune protection against microbial infections. Immunoglobulin preparations designed for farm animals are commercially available, and some colostrumbased products are marketed also for humans as dietary supplements. The concentration of specific antibodies against a certain pathogenic microorganism can be raised in colostrum and milk by immunizing cows with this pathogen or its antigen. Advances in bioseparation and chromatographic techniques have made it possible to fractionate and enrich these antibodies and formulate so-called hyperimmune colostral or milk preparations. Their efficacy in prevention and treatment of various microbial infections has been evaluated in numerous studies. Immune milk preparations have proven effective in prophylaxis against infections caused by a variety of gastrointestinal pathogens. Their therapeutic efficacy, however, seems more limited. A few commercial immune milk products are already on market and more applications can be expected in the coming years. This article reviews the recent progress made in isolation techniques of bovine immunoglobulins and the application of colostral and immune milk preparations in fighting various microbial infectious diseases in humans. r
Output: Milk immunoglobulins for health promotion
The newly identified coronavirus known as 2019-nCoV has Background: posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people globally and led to deaths of more than 1,016 people in China. The 2019 novel coronavirus proteome was aligned to a curated Methods: database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0. We report identification of a comprehensive list of Results: in silico immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential. Given the limited time and resources to develop vaccine and Conclusions: treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.
Output: Open Peer Review identification of vaccine targets for 2019-nCoV In silico [version 1; peer review: 2 approved] , The Francis Crick v1
We analyze the temporal evolution of accumulated hospitalization cases due to COVID-19 in Belgium. The increase of hospitalization cases is consistent with an initial exponential phase, and a subsequent power law growth. For the latter, we estimate a power law exponent of ≈ 2.2, which is consistent with growth kinetics of COVID-19 in China and indicative of the underlying small world network structure of the epidemic. Finally, we fit an SIR-X model to the experimental data and estimate the effect of containment policies in comparison to their effect in China. This model suggests that the base reproduction rate has been significantly reduced, but that the number of susceptible individuals that is isolated from infection is very small. Based on the SIR-X model fit, we analyze the COVID-19 mortality and the number of patients requiring ICU treatment over time.
Output: Scaling analysis of COVID-19 spreading based on Belgian hospitalization data
Coronaviruses are positive-strand RNA viruses that translate their genome RNA into polyproteins that are co-and posttranslationally processed into intermediate and mature replicase nonstructural proteins (nsps). In murine hepatitis virus (MHV), nsps 1, 2, and 3 are processed by two papain-like proteinase activities within nsp3 (PLP1 and PLP2) to yield nsp1, an nsp2-3 intermediate, and mature nsp2 and nsp3. To determine the role in replication of processing between nsp2 and nsp3 at cleavage site 2 (CS2) and PLP1 proteinase activity, mutations were engineered into the MHV genome at CS2, at CS1 and CS2, and at the PLP1 catalytic site, alone and in combination. Mutant viruses with abolished cleavage at CS2 were delayed in growth and RNA synthesis but grew to wild-type titers of >10 7 PFU/ml. Mutant viruses with deletion of both CS1 and CS2 exhibited both a delay in growth and a decrease in peak viral titer to ϳ10 4 PFU/ml. Inactivation of PLP1 catalytic residues resulted in a mutant virus that did not process at either CS1 or CS2 and was severely debilitated in growth, achieving only 10 2 PFU/ml. However, when both CS1 and CS2 were deleted in the presence of inactivated PLP1, the growth of the resulting mutant virus was partially compensated, comparable to that of the CS1 and CS2 deletion mutant. These results demonstrate that interactions of PLP1 with CS1 and CS2 are critical for protein processing and suggest that the interactions play specific roles in regulation of the functions of nsp1, 2, and 3 in viral RNA synthesis.
Output: Replication of Murine Hepatitis Virus Is Regulated by Papain-Like Proteinase 1 Processing of Nonstructural Proteins 1, 2, and 3 ᰔ
Community-acquired respiratory viruses (CARVs) are common pathogens in lung transplant recipients. Infection due to these viruses is associated with multiple complications including: rhinitis, pharyngitis, bronchitis, pneumonia, respiratory failure and even death. CARVs have also become increasingly recognized as a risk factor for acute rejection (AR) and bronchiolitis obliterans syndrome (BOS). Newer diagnostic techniques have enhanced the accuracy of diagnosis, but proven treatment options for CARVs are limited. Further insight into the immune response and allograft dysfunction associated with CARV infections is needed in order to develop novel management strategies which can reduce the morbidity and mortality caused by these infectious agents.
Output: Respiratory viral infections post-lung transplantation
We compared the FilmArray RP (Idaho Technology, Inc., Salt Lake City, UT) and the xTAG RVP (Luminex Corporation, Toronto, Canada) multiplex respiratory virus PCR methods for the detection of respiratory viruses in a set of 200 patient specimens frozen at ؊70°C after standard viral culture and antigen detection methods were done. Both systems detected between 40 to 50% more viruses than traditional methods, primarily rhinoviruses and human metapneumovirus. The FilmArray RP detected significantly more total viruses either alone or as part of mixed infections than the xTAG RVP, as well as an additional 21.6% more respiratory syncytial viruses. The xTAG RVP requires 5 to 6 h with 2.5 to 3 h of hands-on time, while the FilmArray RP takes about an hour with 3 to 5 min of hands-on time, making it much easier to perform.
Output: Comparison of Two Multiplex Methods for Detection of Respiratory Viruses: FilmArray RP and xTAG RVP ᰔ †
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Figure 57-1 Functional anatomy of the small intestine. A, Anatomic arrangement of the small intestine. B, The small intestine is basically a tube with a serosal surface covered by visceral peritoneum and an inner absorptive and digestive surface, the mucosa. C, Beneath the outer serosa, longitudinal and circular muscle layers produce peristaltic and segmental contractions for propelling and mixing the luminal contents. The submucosa is rich in blood and lymphatic vessels. The mucosa comprises the thin muscularis mucosa, the lamina propria, and the columnar epithelium; it is thrown into folds and is covered by finger-like villi to increase the digestive and absorptive surface area. D, Enterocytes, which are shed from the villus tip but are continually replaced through division of crypt cells, are the site of nutrient digestion and absorption. Goblet cells secrete protective mucus. Water-soluble nutrients pass into the rich capillary network of the lamina propria, and fat is passed as chylomicrons into the lacteals. Immunocytes in the lamina propria are involved in maintaining tolerance to luminal antigens. E, The luminal membrane of the enterocyte is thrown into processes called microvilli, which increase the luminal surface area. Tight junctions between enterocytes maintain epithelial integrity. Absorbed nutrients are passed from the enterocyte into the intercellular space for distribution to the body. F, Schematic of a microvillus showing digestive hydrolases anchored in the phospholipid cell membrane and protruding into the intestinal lumen. Carrier proteins in the membrane are believed to act as "pores," shuttling nutrients across the membrane by means of conformational changes in their structure often induced by sodium influx at the expense of energy utilization through Na/K-adenosine triphosphatase (ATPase) on the basolateral membrane.
Output: Small Intestine STRUCTURE AND FUNCTION
Single-sided natural ventilation was numerically investigated to determine the impact of buoyancy and wind on the cross-transmission of pollution by considering six window types commonly found in multistory buildings. The goal of this study was to predict the gaseous pollutant transmission using computational fluid dynamics based on the Reynolds-averaged Navier-Stokes equations and baseline k-ω turbulence equations. The results indicated that ventilation rates generally increased with increasing wind speeds if the effects of buoyancy and wind were not suppressed; however, the re-entry ratio representing the proportion of expelled air re-entering other floors and the corresponding risk of infection decreased. If the source of the virus was on a central floor, the risk of infection was the highest on the floors closest to the source. Different window types were also considered for determining their effectiveness in controlling cross-transmission and infection risk, depending on the source location and driving force (e.g., buoyancy and wind).
Output: Numerical investigation of gaseous pollutant cross-transmission for single-sided natural ventilation driven by buoyancy and wind
The capsids of most plant viruses are simple and robust structures consisting of multiple copies of one or a few types of protein subunit arranged with either icosahedral or helical symmetry. In many cases, capsids can be produced in large quantities either by the infection of plants or by the expression of the subunit(s) in a variety of heterologous systems. In view of their relative simplicity, stability and ease of production, plant virus particles or virus-like particles (VLPs) have attracted attention as potential reagents for applications in bionanotechnology. As a result, plant virus particles have been subjected to both genetic and chemical modification, have been used to encapsulate foreign material and have, themselves, been incorporated into supramolecular structures.
Output: Applications of Plant Viruses in Bionanotechnology
Waumans Y, Baerts L, Kehoe K, Lambeir A-M and De Meester I (2015) The dipeptidyl peptidase family, prolyl oligopeptidase, and prolyl carboxypeptidase in the immune system and inflammatory disease, including atherosclerosis. Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease. Keywords: dipeptidyl peptidase, prolyl oligopeptidase, fibroblast activation protein α α α, prolyl carboxypeptidase, inflammation, immunophysiology, atherosclerosis Frontiers in Immunology | www.frontiersin.org August 2015 | Volume 6 | Article 387 FIGURE 1 | The DPP family. Summary of the names, the localization, and most important field of action of all members of the DPP family.
Output: The dipeptidyl peptidase family, prolyl oligopeptidase, and prolyl carboxypeptidase in the immune system and inflammatory disease, including atherosclerosis
Investigation of the secondary metabolites of the ascidian Herdmania momus led to the isolation and characterization of four new nucleoside derivatives (1) (2) (3) (4) . Structural studies showed that these derivatives represent a series of rare methylsulfinyladenosine derivatives of interconvertible transesterification isomers and/or sulfinyl epimers. The antiviral activities of these rare nucleosides were evaluated against a series of human pathogenic viruses. Marine ascidians are a rich source of chemically diverse secondary metabolites, with remarkable biological activities. 1,2 such as amino acid derivatives and complex alkaloids. [3] [4] [5] [6] [7] [8] [9] In our previous study on bioactive compounds from the solitary tunicate Herdmania momus, a series of amino acid derivatives (herdmanines A-M) were isolated. 3,4 As a part of continuing study on the metabolites of the same tunicate, four new complex nucleosides (1-4) containing the rare methylsulfinyladenosine were isolated. Details of the isolation, structure elucidation, and of the results of the antiviral screening of these metabolites are described herein. The combined MeOH and CH 2 Cl 2 extracts were sequentially partitioned between CH 2 Cl 2 and H 2 O, and n-BuOH and H 2 O. The n-BuOH-soluble fraction was subjected to chromatographic separation and purification to yield a series of nucleoside derived metabolites (1-4). 10 Compounds 1 and 2 were found to be interconvertible, and on standing at room temperature after HPLC separation, each compound afforded the same equilibrium ratio of compound 1-2 (56:44). Compounds 3 and 4 were also interconvertible, and on standing at room temperature produced an identical equilibrium mixture (56:44) as that of 1 and 2. Spectral analysis of these interconvertible compounds was performed on equilibrium mixtures. The equilibrium mixture of compounds 1 and 2 was a white powder. The (+)-FABMS spectrum of this mixture showed isotopic peaks of [M+2H] + and [M+3H] + at m/z 554/552 and 555/553, respectively, with an isotopic peak ratio of 1:1. This pseudomolecular ionic configuration is shared with various other nucleosides N N N N NH 2
Output: Epimeric methylsulfinyladenosine derivatives from the marine ascidian Herdmania momus
Objectives The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-ofcare testing (POCT). Methods We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing. Results 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline. Conclusions The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.
Output: Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment
Background: We performed an assessment of an independent rapid flu clinic service (RFCS) unit, which was set up outside the emergency department (ED) during the 2009 H1N1 pandemic season. The unit was able to relieve the crowding of regular ambulatory and emergency services. Methods: Between August and December 2009, a total of 6,152 patients with influenza-like illness were enrolled in this observational retrospective study. Patients with positive influenza tests were interviewed to evaluate the efficiency of RFCS. Results: The mean length of stay (LOS) for the RFCS was 50 minutes, which was shorter than the LOS for ambulatory services (1 hour) and regular ED services (3.5 hours). Overall, 88% of patients were satisfied with the RFCS. Of 6,152 patients receiving flu tests, 1,235 (20%) had a positive result. Fever (odds ratio [OR], 4.28, 95% confidence interval [CI]: 3.11-5.89), fever combined with cough and sore throat (OR, 2.52; 95% CI: 2.18-2.92), fever combined with sore throat (OR, 2.42; 95% CI: 2.13-2.75), history of contacting confirmed flu patients within 7 days (OR, 2.40; 95% CI: 2.07-2.78), fever combined with cough (OR, 2.19; 95% CI: 1.92-2.47), sore throat (OR, 2.03, 95% CI: 1.79-2.30); and cough (OR, 1.91, 95% CI: 1.69-2.17) were significantly associated with positive influenza tests. Conclusion: Setting up the RFSC was beneficial to health care facilities during a pandemic flu season.
Output: Impacts of rapid flu clinic services at an emergency department during the pandemic flu season
Recently, indoor air quality (IAQ) has become an important issue as it affects people's comfort and health. To mitigate the problem, application of some innovative air filtering devices has been generally recognized as one of the effective ways. This study adopted an action research-dominated approach to test whether the indoor air quality in the tested hotel rooms meets the recognized standard, and measure the pollutant removal efficiency of three types of air purifiers. Focus group discussion was carried out to ascertain the difference in hotel managers' understanding of indoor air quality research before the experiment and management response after the experiment. The result of field test indicates that the actual performance of the purifiers is not as good as the manufactures claim. The management response study also ascertains that hotel department heads' awareness, exposure and training in relation to IAQ testing is limited.
Output: Management learning from air purifier tests in hotels: Experiment and action research ଝ
Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized. Objective. To assess the spectrum of illness in health-care workers (HCWs). A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay. Results. A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS. Conclusions. Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter.
Output: Mild Illness Associated with Severe Acute Respiratory Syndrome Coronavirus Infection: Lessons from a Prospective Seroepidemiologic Study of Health-Care Workers in a Teaching Hospital in Singapore
Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH 4 Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC 50 of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/ cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.
Output: Virology Journal Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses
Blood parasites of the sub-genus Haemoproteus have been reported in seabirds, in particular in species in the Suliformes order. These parasites are transmitted by hippoboscid flies of the genus Olfersia; strong specificity has been suggested between the vector and its vertebrate host. We investigated the prevalence of Haemoproteus infection in Suliformes and hippoboscid flies in two oceanic islands of the Western Indian Ocean: Europa and Tromelin. In total, 209 blood samples were collected from great frigatebirds (Fregata minor), masked boobies (Sula dactylatra) and red-footed boobies (Sula sula). Fortyone hippoboscid flies were also collected from birds. Seventeen frigatebirds and one fly collected on Europa tested positive for the presence of Haemoproteus parasites by polymerase chain reaction. Phylogenetic analyses based on partial sequences of the Cytochrome b gene showed that parasites were closely related to Haemoproteus iwa reported from frigatebirds in the Pacific Ocean and in the Caribbean. Plasmodium was also detected in a frigatebird on Europa; however, its placement on the phylogenetic tree could not be resolved. We provide strong support for transmission of blood parasites in seabirds in the Western Indian Ocean and suggest that migrations between the Pacific and the Indian oceans could favor the large-scale distribution of Haemoproteus iwa in frigatebird populations. Citation: Bastien M, Jaeger A, Le Corre M, Tortosa P, Lebarbenchon C (2014) Haemoproteus iwa in Great Frigatebirds (Fregata minor) in the Islands of the Western Indian Ocean. PLoS ONE 9(5): e97185.
Output: Haemoproteus iwa in Great Frigatebirds (Fregata minor) in the Islands of the Western Indian Ocean
Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with T H 1 and T H 2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results: Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion: These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression. (J Allergy Clin Immunol 2019;144:1551-65.)
Output: Decreased expression of type I (IFN-b) and type III (IFN-l) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps
Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.
Output: Clinical Medicine Review Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections
Background: A novel strain of influenza A (H1N1) was identified in April 2009 and developed into a pandemic by June 2009. This rapid and unexpected event had enormous implications for infection preventionists (IP) internationally. Lessons learned from this event should guide future pandemic planning efforts. Methods: Focus groups were conducted at the Association for Professionals in Infection Control and Epidemiology, Inc, (APIC) 2009 conference to evaluate IPs' experience with the novel H1N1 influenza pandemic and assess their perceived needs related to novel H1N1 topics and products required for future education and reference materials. Results: Forty IPs (37 from the United States and 3 international) participated in the focus groups. Needed reference materials identified by attendees included infection prevention guidance for nonacute care settings; occupational health polices; and brief, multilanguage patient/family educational materials. Educational topics on which IPs need to be trained include isolation precautions/ personal protective equipment recommendations for novel H1N1 patients, coordination between hospitals and community response agencies, and surge management. The rapidly changing and conflicting recommendations related to patient management made responding to this event challenging. IPs require synthesized infection prevention guidelines developed in a concise, real-time format. Conclusion: IPs must continue to partner with public health and other response agencies to address gaps in pandemic planning.
Output: Infection preventionists' experience during the first months of the 2009 novel H1N1 influenza A pandemic
The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30-74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PP i exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme. . Table S1 lists the amino acid sequence numbering for the different subdomains, motifs A-G, and functional regions I-III of the RdRps used in the study. Figure S1 shows the structure-based sequence alignment for the different RdRps. Figure S2 shows the time series plot of RMSD for the different simulated systems. Figure S3 shows representative structures for the clusters C1-C4 of PV RdRp in two views. Figure S4 shows snapshots corresponding to the beginning, middle, and end of the simulation trajectories of the four RdRps. Figure S5 compares analyzed B-factors for the different simulated RdRps. Figure S6 compares the per-residue RMSD analysis for the different simulated RdRps. Figure S7 compares the radius of gyration analysis for the different RdRps. Figure S8 compares the RNA channel width in the different simulated RdRps. Figure S9 compares PCA and DCCM analyses from 25 and 52 ns simulations of PV RdRp. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.
Output: Author manuscript; available in PMC
Neonatal calf diarrhea is a multi-etiology syndrome of cattle and direct detection of the two major agents of the syndrome, group A rotavirus and Bovine coronavirus (BCoV) is hampered by their fastidious growth in cell culture. This study aimed at developing a multiplex semi-nested RT-PCR for simultaneous detection of BCoV (N gene) and group A rotavirus (VP1 gene) with the addition of an internal control (mRNA ND5). The assay was tested in 75 bovine feces samples tested previously for rotavirus using PAGE and for BCoV using nested RT-PCR targeted to RdRp gene. Agreement with reference tests was optimal for BCoV (kappa = 0.833) and substantial for rotavirus detection (kappa = 0.648). the internal control, ND5 mRNA, was detected successfully in all reactions. Results demonstrated that this multiplex semi-nested RT-PCR was effective in the detection of BCoV and rotavirus, with high sensitivity and specificity for simultaneous detection of both viruses at a lower cost, providing an important tool for studies on the etiology of diarrhea in cattle.
Output: Multiplex semi-nested RT-PCR with exogenous internal control for simultaneous detection of bovine coronavirus and group A rotavirus
Background: The widespread forest fires in Indonesia in June 2013 led to widespread haze to neighbouring countries. This is the first study in the medical literature reporting the acute physical and psychological symptoms of the general population during a haze crisis. We evaluated the factors that are associated with psychological stress of haze exposure. Methods: This study was conducted between June 21 to June 26, 2013. Participants were recruited by an online recruitment post and snowball sampling techniques. Participants were required to complete an online survey which was composed of demographics questionnaire, physical symptom checklist, perceived dangerous Pollutant Standard Index (PSI) value and views on the N-95 mask and the Impact of Event Scale-Revised (IES-R). Results: A total of 298 participants returned the completed study questionnaire. The respondents reported a mean number of 4.03 physical symptoms (S.D. = 2.6). The five most common physical symptoms include mouth or throat discomfort (68.8%), nose discomfort (64.1%), eye discomfort (60.7%), headache (50.3%) and breathing difficulty (40.3%). The total IES-R score was 18.47 (S.D. = 11.69) which indicated that the study population experienced mild psychological stress but not to the extent of acute stress reaction syndrome. The perceived dangerous PSI level and number of physical symptoms were significantly associated with the mean intrusion score, mean hyper-arousal score, total mean IES-R score and total IES-R score (p < 0.05). Conclusions: Our findings suggest that a haze crisis is associated with acute physical symptoms and mild psychological stress. The number of physical symptoms and the perceived dangerous PSI values are important factors associated with psychological stress.
Output: Impact of 2013 south Asian haze crisis: study of physical and psychological symptoms and perceived dangerousness of pollution level
Amiodarone [2-butyl-3-(3#,5#-diiodo-4'a-diethylaminoethoxybenzoyl)-benzofuran] (AMD), a class III antiarrhythmic drug, is known to cause idiosyncratic hepatotoxic reactions in human patients. One hypothesis for the etiology of idiosyncratic adverse drug reactions is that a concurrent inflammatory stress results in decreased threshold for drug toxicity. To explore this hypothesis in an animal model, male Sprague-Dawley rats were treated with nonhepatotoxic doses of AMD or its vehicle and with saline vehicle or lipopolysaccharide (LPS) to induce low-level inflammation. Elevated alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities as well as increased total bile acid concentrations in serum and midzonal hepatocellular necrosis were observed only in AMD/LPS-cotreated rats. The time interval between AMD and LPS administration was critical: AMD injected 16 h before LPS led to liver injury, whereas AMD injected 2-12 h before LPS failed to cause this response. The increase in ALT activity in AMD/LPS cotreatment showed a clear doseresponse relationship with AMD as well as LPS. The metabolism and hepatic accumulation of AMD were not affected by LPS coexposure. Serum concentration of tumor necrosis factor-alpha (TNF) was significantly increased by LPS and was slightly prolonged by AMD. In Hepac1c7 cells, addition of TNF potentiated the cytotoxicity of both AMD and its primary metabolite, mono-N-desethylamiodarone. In vivo inhibition of TNF signaling by etanercept attenuated the AMD/LPS-induced liver injury in rats. In summary, AMD treatment during modest inflammation induced severe hepatotoxicity in rats, and TNF contributed to the induction of liver injury in this animal model of idiosyncratic AMD-induced liver injury.
Output: Amiodarone Exposure During Modest Inflammation Induces Idiosyncrasy-like Liver Injury in Rats: Role of Tumor Necrosis Factor-alpha
Several mathematical models of epidemic cholera have recently been proposed in response to outbreaks in Zimbabwe and Haiti. These models aim to estimate the dynamics of cholera transmission and the impact of possible interventions, with a goal of providing guidance to policymakers in deciding among alternative courses of action, including vaccination, provision of clean water, and antibiotics. Here we discuss concerns about model misspecification, parameter uncertainty, and spatial heterogeneity intrinsic to models for cholera. We argue for caution in interpreting quantitative predictions, particularly predictions of the effectiveness of interventions. We specify sensitivity analyses that would be necessary to improve confidence in model-based quantitative prediction, and suggest types of monitoring in future epidemic settings that would improve analysis and prediction. The recent cholera epidemic in Zimbabwe (2008)(2009) and the ongoing cholera epidemic in Haiti (2010-2011) are catastrophes in two regions already devastated by disease and poverty. The extent of these disasters has prompted inquiries into whether interventions -such as vaccination, antibiotic administration, and the provision of clean water -could have slowed or aborted these cholera epidemics, and how such interventions might be most effectively implemented in future epidemics. Cholera spreads in areas with poor sanitation and through contaminated water, and the ideal solution is to improve infrastructure to provide clean water and effective sanitation --an approach that has been successful since the 19 th century. 1 On the timescale of an epidemic, creation of such infrastructure is rarely feasible. Administration of vaccine, a staple of preventive medicine, is one of the few potentially life-5 Corresponding author: Marc Lipsitch, Professor of Epidemiology,
Output: Cholera Modeling: Challenges to Quantitative Analysis and Predicting the Impact of Interventions NIH Public Access