niryuu/sni-each-converted huggingface dataset:
We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE-deleted isogenic mutants, a 40% (p=0.001) and 42% (p=0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of E coli and demonstrated that when PhtD and PhtE were surface expressed on E coli adherence increased to D562 and A549 cells, compared with the E coli parent strain (p = 0.005, 0.013 for D562 and p=0.034, p=0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1 μg of IgG Fab from adult sera led to a 34% reduction (p= 0.002) and from children a 20% (p= 0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera, the depletion of PhtD and PhtE specific Fab from total IgG Fab resulted in a significant increase in the number of D562 epithelial cells with adherent pneumococci (p=0.005 for PhtD and p=0.024 for PhtE). We conclude that antibody directed to PhtD and PhtE are adhesins of pneumococci, if raised by vaccination, may function to prevent pneumococcal adherence to human airway epithelial cells.
Output: Vaccine Candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans
Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based on highthroughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host-pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. Most surprisingly, this approach has also revealed a new mechanism of diversification based on templated insertion of non-Ig DNA into antibody genes that we discovered in the context of the immune response to malaria infection.
Output: Louis-Jeantet Prize Winner: Commentary Dissecting human antibody responses: useful, basic and surprising findings
Background-The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8,000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. Methods-A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays. The vaccine was well-tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T cell responses were detected in all vaccinees, and CD8+ T cell responses in ∼20% of individuals. Conclusions-The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.
Output: A SARS DNA Vaccine Induces Neutralizing Antibody and Cellular Immune Responses in Healthy Adults in a Phase I Clinical Trial
Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against a feline coronavirus in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC 50 in a nanomolar range) and, furthermore, combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in a cell culture system.
Output: Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease
Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children. We followed 217 children from birth to 1 year of age. Nasal swabs and symptom diaries were collected monthly. Anti-hMPV and anti-RSV IgG antibodies by age 1 year were detected by ELISA, and nasal swabs were analysed for hMPV and RSV by RT-PCR. Logistic regression was used for risk factor analysis. Anti-hMPV IgG was found in 38 children (17.5%), and anti-RSV IgG in 172 children (79%). Risk factors for being anti-hMPV IgG-positive were: (1) being born in the spring (OR =2.36; 95% CI:1.06-5.27), and (2) having older siblings (OR=3.82; 95% CI:1.75-8.34). Risk factors for being anti-RSV IgG-positive were: (1) gestational age <38 weeks (OR=3.39; 95% CI:1.42-8.05), (2) increasing paternal age (OR=1.85 per 5 yrs; 95% CI:1.28-2.68), and (3) wall-to-wall carpeting (OR=3.15; 95% CI:1.29-7.68). Being born in the spring was associated with decreased odds of being anti-RSV IgG-positive (OR=0.27, 95% CI:0.09-0.85). Risk factors for RSV hospitalisation (n= 11) were: (1) older siblings (OR=4.49; 95% CI: 1.08-18.73) and (2) smoking in the household (OR=5.06; 95% CI: 1.36-18.76). Exclusive breastfeeding for the first 14 days of life protected against hospitalisation (OR= 0.21; 95% CI:0.06-0.79). In conclusion, this study identifies risk factors for mild and asymptomatic hMPV infections in infancy. Abbreviations hMPV human metapneumovirus RSV respiratory syncytial virus OR odds ratio PBS phosphate-buffered saline NPA nasopharyngeal aspirate RT-PCR reverse transcription-polymerase chain reaction ELISA enzyme-linked immunosorbent assay RT room temperature M-PBS PBS with 2% skim-milk powder HRP horseradish peroxidase TMB tetramethyl benzidine OD optical density SD standard deviation PDV Phocine Distemper Virus Eur
Output: A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life
Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. Approximately 15 million (>25%) of 57 million deaths per year worldwide are estimated to be related directly to infectious diseases [1] . Vaccination is considered to be the most efficient and cost-effective means for health intervention to combat infectious diseases. However, the high cost of vaccination makes it unaffordable for most people living in developing countries, as the daily average income for nearly one billion people is <US$1. A 14-fold increase in the cost of vaccines over the past decade [2] makes it necessary to investigate alternate strategies for their production and delivery. Also, with an emphasis on safety, there has been an increasing shift towards the development of subunit vaccines (that use one or two proteins instead of avirulent or killed pathogen strains), with reliance on recombinant expression systems. The high cost of current vaccines and biopharmaceuticals is largely due to their complex production and delivery methods, including the significant costs of fermentation and purification systems and additional expenses associated with adjuvant, cold storage, transportation and sterile delivery. No viable alternative to fermentation technology has yet emerged for their mass production, a void that could be addressed through the use of plants as bioreactors for the production and oral delivery of therapeutic proteins. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear, transient viral and
Output: Plant-made vaccine antigens and biopharmaceuticals Need for a new platform for production of therapeutic proteins NIH Public Access Plant-made therapeutic proteins -current status and challenges ahead
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. Arch Bronconeumol. 2016;52(5):269-273 w w w . a r c h b r o n c o n e u m o l . o r g a b s t r a c t Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1 year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40 years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.
Output: Pediatric Asthma and Viral Infection ଝ
Background. The severe acute respiratory syndrome (SARS) epidemic that occurred in Hong Kong in 2003 caused serious public health consequences. Its impacts on health-seeking behaviors of the general public have not been assessed. Methods. Two cross-sectional, random telephone surveys interviewed 1603 Hong Kong adult residents in the post-SARS epidemic period, June and September 2003 to investigate changes in the post-SARS period. Results. Noteworthy percentages of the respondents self-reported increased frequencies of practicing favorable health-seeking behaviors in June 2003, as compared with the pre-SARS period. Few respondents reported the opposite. This was observed in different dimensions: health services seeking, adoption of healthier lifestyle, spending more resources on health, adoption of good personal hygiene, mask use when ill with influenza, and avoidance of risk behaviors. The frequencies of practicing most of these health-seeking behaviors, as measured in June and September 2003, were comparable. Further increases in healthy diet and weight control, etc., were observed during that period. Those who worried about contracting SARS were more likely to have improved health-seeking behaviors. Conclusions. The community in Hong Kong responded to the SARS epidemic by practicing more favorable health-seeking behaviors. Public health workers should utilize these opportunities to foster favorable changes. D
Output: Impacts of SARS on health-seeking behaviors in general population in Hong Kong
Background: Since 2010, outbreaks of genotype 2 (G2) porcine epidemic diarrhea virus (PEDV) have caused high mortality in neonatal piglets and have had devastating impacts on the swine industry in many countries. A reliable serological assay for evaluating the PEDV-specific humoral and mucosal immune response is important for disease survey, monitoring the efficacy of immunization, and designing strategies for the prevention and control of PED. Two PEDV spike (S) glycoprotein-based indirect enzyme-linked immunosorbent assays (ELISAs) were developed using G2b PEDV-Pintung 52 (PEDV-PT) trimeric full-length S and truncated S 1-501 proteins derived from the human embryonic kidney (HEK)-293 cell expression system. The truncated S 1-501 protein was selected from a superior expressed stable cell line. The sensitivity and specificity of these two ELISAs were compared to immunostaining of G2b PEDV-PT infected cells and to a commercial nucleocapsid (N)-based indirect ELISA kit using a panel of PEDV negative and hyperimmune sera. The commercial N-based ELISA exhibited a sensitivity of 37%, a specificity of 100%, and a fair agreement (kappa = 0.37) with the immunostaining result. In comparison, the full-length S-based ELISA showed a sensitivity of 97.8%, a specificity of 94%, and an almost perfect agreement (kappa = 0.90) with the immunostaining result. Interestingly, the S 1-501 -based ELISA had even higher sensitivity of 98.9% and specificity of 99.1%, and an almost perfect agreement (kappa = 0.97) with the immunostaining result. A fair agreement (kappa< 0.4) was seen between the commercial N-based ELISA and either of our S-based ELISAs. However, the results of the full-length S-based ELISA shared an almost perfect agreement (kappa = 0.92) with that of S 1-501 -based ELISA. (Continued on next page)
Output: Development and comparison of enzyme- linked immunosorbent assays based on recombinant trimeric full-length and truncated spike proteins for detecting antibodies against porcine epidemic diarrhea virus
By using a nested case-control design, the authors studied the effectiveness of the influenza vaccine in reducing severe and fatal complications in 4,241 and 5,966 primary care, working-age patients aged 18-64 years who had asthma or chronic obstructive pulmonary disease during the 1998-1999 and 1999-2000 influenza epidemics in the Netherlands. Patients developing fatal or nonfatal exacerbations of lung disease, pneumonia, congestive heart failure, or myocardial infarction during either epidemic were considered cases. For each case, four age-and sex-matched controls were randomly sampled, and patient records were reviewed. Conditional logistic regression and propensity scores were used to assess vaccine effectiveness after adjustment for confounding factors. In seasons one and two, respectively, 87% (47/54) and 85% (171/202) of the cases and 74% (155/210) and 75% (575/766) of the controls had been vaccinated. After adjustments, vaccination was not associated with reductions in complications (season one: odds ratio = 0.95, 95% confidence interval (CI): 0.26, 3.48; season two: odds ratio = 1.07, 95% CI: 0.59, 1.96; pooled odds ratio = 1.07, 95% CI: 0.63, 1.80). Because influenza vaccination appeared not to be associated with a clinically relevant reduction in severe morbidity, other measures need to be explored. case-control studies; immunization; influenza; lung diseases; middle age; vaccines Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease.
Output: Conventional Influenza Vaccination Is Not Associated with Complications in Working-Age Patients with Asthma or Chronic Obstructive Pulmonary Disease
Introduction: We report the results of the active surveillance of influenza infections in hospitalized patients and the evaluation of the seasonality and correlation with temperature and rainfall data. Methods: During the 2-year study period, 775 patients were tested for 15 respiratory viruses (RVs). Results: Most of the 57% of (n=444) virus-positive samples were human rhinovirus and respiratory syncytial virus. However, 10.4% (n=46) were influenza virus (80% FluA; 20% FluB). Age and SARI were significantly associated with influenza. FluB circulation was higher is 2013. Conclusions: In the post-epidemic period, influenza remains an important cause of hospitalization in SARI patients.
Output: Short Communication Revista da Sociedade Brasileira de Medicina Tropical Influenza Sentinel Surveillance and Severe Acute Respiratory Infection in a Reference Hospital in Southern Brazil
Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral 'fusion proteins' facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. We describe three examples-the influenza virus hemagglutinin, the flavivirus E protein and the vesicular stomatitis virus G protein-in some detail, to illustrate the ways in which different structures have evolved to implement this common mechanism. Fusion inhibitors can be effective antiviral agents. 'Enveloped' viruses-those with lipid bilayers as integral parts of their structure-enter the cells they infect by fusion of viral and host-cell membranes. One or more viral membrane proteins facilitate the various fusion steps. Several such fusion proteins have now been studied in great detail, with crystal structures determined for both the form of the protein present on the viral surface before interaction with the cell ('pre-fusion' conformation) and the form of the protein after fusion is complete ('post-fusion' conformation). The proteins show a variety of molecular architectures, but what we can infer from the various structures and from experiments both in solution and with cells suggests that all of them catalyze fusion in essentially the same way. We can even draw a rough analogy to serine proteases, which can have very different polypeptide chain folds but identical active-site mechanisms.
Output: Viral membrane fusion
A new species of parvovirus, tentatively named human bocavirus 4 (HBoV4), was genetically characterized. Among 641 feces samples obtained from children and adults, the most commonly detected bocavirus species were, in descending order, HBoV2, HBoV3, HBoV4, and HBoV1, with an HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children, respectively. HBoV3 or HBoV4 species were found in 12 of 192 patients with non-polio acute flaccid paralysis in Tunisia and Nigeria and 0 of 96 healthy Tunisian contacts (P p ). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within bocavirus .01 species was found. The high degree of genetic diversity seen among the human bocaviruses found in feces specimens, relative to the highly homogeneous HBoV1, suggest that this worldwide-distributed respiratory pathogen may have recently evolved from an enteric bocavirus after acquiring an expanded tropism favoring the respiratory tract. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases, including acute flaccid paralysis and diarrhea, will require further epidemiological studies. Parvoviruses are small, non-lipid-enveloped, environmentally resistant viral particles with single-stranded linear DNA genomes that frequently infect animals through the fecal-oral route [1] . Parvoviruses can cause numerous symptoms in animals, including enteritis, panleukopenia, hepatitis, erythrocyte aplasia, and cerebellar ataxia [1]. Efficacious vaccines against animal parvovirus infections are widely employed [2] [3] [4] . Following the identification of the human parvovirus
Output: Human Bocaviruses Are Highly Diverse, Dispersed, Recombination Prone, and Prevalent in Enteric Infections
In the wake of COVID-19 disease, caused by the SARS-CoV-2 virus, we designed and developed a predictive model based on Artificial Intelligence (AI) and Machine Learning algorithms to determine the health risk and predict the mortality risk of patients with COVID-19. In this study, we used documented data of 117,000 patients world-wide with laboratory-confirmed COVID-19. This study proposes an AI model to help hospitals and medical facilities decide who needs to get attention first, who has higher priority to be hospitalized, triage patients when the system is overwhelmed by overcrowding, and eliminate delays in providing the necessary care. The results demonstrate 93% overall accuracy in predicting the mortality rate. We used several machine learning algorithms including Support Vector Machine (SVM), Artificial Neural Networks, Random Forest, Decision Tree, Logistic Regression, and K-Nearest Neighbor (KNN) to predict the mortality rate in patients with COVID-19. In this study, the most alarming symptoms and features were also identified. Finally, we used a separate dataset of COVID-19 patients to evaluate our developed model accuracy, and used confusion matrix to make an in-depth analysis of our classifiers and calculate the sensitivity and specificity of our model.
Output: Predicting Mortality Risk in Patients with COVID-19 Using Artificial Intelligence to Help Medical Decision-Making
This study applied a financial portfolio theory to estimate optimal market mixes to minimize the instability of inbound tourist market demand. An empirical analysis was applied to inbound tourists to Taiwan. The results shed light on diversification in tourism market and offer tourism authorities and policy-makers explicit guidelines for risk management in the destination planning process. Specifically, using optimal mixes with various return/risk options can facilitate a more stable pattern of arrivals from foreign countries. To achieve the Doubling Tourist Arrivals Plan, introduced by the Taiwanese government in 2002, the tourism authorities should take the high-return/ high-risk option and shift available resources to Japan. More policy implications are provided to guide tourism authorities and policy makers. r
Output: Financial portfolio approach to optimal tourist market mixes
Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models. However, at present, no treatment yet reached validation to be used in the clinical practice, although several drugs are currently tested in clinical trials for their ability to improve muscle metabolism in cancer patients. Along this line, the results obtained in both experimental and clinical studies clearly show that cachexia can be effectively approached by a multidirectional strategy targeting nutrition, inflammation, catabolism, and inactivity at the same time. In the present study, approaches aimed to modulate muscle metabolism in cachexia will be reviewed.
Output: Modulating Metabolism to Improve Cancer-Induced Muscle Wasting
Porcine epidemic diarrhea (PED) is an emerging disease of pigs in several countries. In the present study, individual sow productivity of Berkshire sows exposed to PED virus at different stages of production was compared. On a commercial farrow-to-finish farm in Kagoshima Prefecture, Japan, the clinical presence of PED was observed in the farrowing barn on January 6, 2014, and all gilts and sows were immunized on January 9, except those in the farrowing barn. The sows were categorized into six groups based on the period in which they were exposed to PED virus: between days 0-30 (G1), 31-60 (G2), 61-90 (G3), or after 91 days of pregnancy (G4), during lactation (L), and after weaning (W). The control group was not exposed to PED during the period of PED outbreak. The study was based on 574 production records. The sows of the G4 and L groups had the fewest piglets weaned (4.8 ± 0.4, and 4.0 ± 0.3 pigs, respectively; P < 0.05) and the greatest pre-weaning mortality (33.1 ± 4.8%, and 39.7 ± 4.1%, respectively; P < 0.05). The number of piglets weaned and pre-weaning mortality, however, did not differ among the G1, G2, G3, and uninfected groups. The G4 and W groups had slightly lesser farrowing rates than the uninfected group (P < 0.05), however, similar subsequent piglet litter performance as the uninfected group. In conclusion, the effect of PED on individual sow productivity differed with the production stage in which sows were exposed to PED virus.
Output: Impact of porcine epidemic diarrhea on herd and individual Berkshire sow productivity
The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin. . 2 The abbreviations used are: C3, C3 exoenzyme derived from Clostridium botulinum; RGD, Arg-Gly-Asp; SARS, severe acute respiratory syndrome; ANOVA, analysis of variance; aa, amino acid(s).
Output: The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif
The development of antimicrobial agents has been a key achievement of modern medicine. However, their overuse has led to an increasing incidence of infections due to antibiotic-resistant microorganisms. Quantitative figures on the current economic and health impact of antimicrobial resistance are scant, but it is clearly a growing challenge that requires timely action. That action should be at the educational, ethical, economic and political level. An important first step would be to increase public awareness and willingness to take the necessary measures to curb resistance. Hence, studies are needed that would provide solid, quantitative data on the societal impact of antibiotic resistance. This review discusses the complexity of resistance, identifies its main drivers and proposes measures to contain it on a European scale. (W.T.M. Jansen). to reports on antibiotic resistance which generally cover a single topic in the field, this review aims to demonstrate the complexity of resistance; identify the main factors involved; propose adequate measures to contain resistance on a European scale.
Output: Bacterial resistance: A sensitive issue Complexity of the challenge and containment strategy in Europe
required for defective interfering RNA replication, subgenomic RNA synthesis, and presumably also for virus genome replication. 1-3 For the BCoV 5' UTR, the minimum free energy structure is predicted to contain three stem-loops. 3 We have analyzed the entire 5' UTR sequences of nine group 1 and group 2 coronaviruses, including the newly discovered SARS and HKU1 coronaviruses, using consensus, covariation secondary structure predictions. Our analysis shows that the predicted secondary structures of all coronavirus 5' UTRs are strikingly similar and contain three or four stem-loops, including a previously unrecognized highly conserved UNR stem-loop. Computer-assisted modeling predicts an invariant and previously unrecognized UNR stem-loop among nine coronavirus UTR sequences, denoted SL2. This predicted conserved structure encompasses nucleotides 42-56 for both MHV and the SARScoronavirus. NMR spectroscopy of the 16-nt RNA SL2 sars reveals spectral features consistent with a UNR hairpin loop. Reverse genetics studies revealed that SL2 is required for MHV replication; MHV genomes containing a substitution of the required U48 with C in the UNR loop (U48C) were not viable. RT-PCR analysis of the U48C mutant indicated that negative sense genome sized RNAs were present in cells electroporated with this mutant; however, neither positive nor negative sense subgenomic RNAs were detected. Mutations that destabilized the stem of SL2 were viable but had moderately to severely impaired replication phenotypes. Mutants that maintained the stem-loop structure replicated similarly to wild-type MHV. These genetic data strongly support the existence of the predicted UNR stem loop and its functional importance in viral replication.
Output: A PREVIOUSLY UNRECOGNIZED UNR STEM-LOOP STRUCTURE IN THE CORONAVIRUS 5' UNTRANSLATED REGION PLAYS A FUNCTIONAL ROLE IN REPLICATION
doi: bioRxiv preprint molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in both pathogenic and attenuated forms of IBV, and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intraspecies variation, with single nucleotide polymorphisms associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. We also identify numerous cellular genes and gene networks that are differentially expressed during virus infection, giving insights into the host cell reponse to IBV infection. 3 47 48 49 50 51 52 53 54 55 56 author/funder. All rights reserved. No reuse allowed without permission.
Output: Comparative analysis of gene expression in virulent and attenuated strains of infectious bronchitis virus at sub-codon resolution
Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8 + and CD4 + T cells, and ␥␦ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFN␥ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGF␤) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.
Output: Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs
The electrochemiluminescence (ECL) behavior of N-(4-aminobutyl)-N-ethylisoluminol (ABEI)-functionalized graphene composite (ABEI-GC) modified on an indium tin oxide (ITO) electrode was studied. ABEI-GC exhibited excellent ECL activity. On this basis, a label-free ECL immunosensor was developed for the sensitive detection of human immunoglobulin G (hIgG) by using ABEI-GC as the ECL nano-interface via a layer-by-layer assembly technique. ABEI-GC was first assembled onto an ITO electrode. Positively charged chitosan was then electrostatically adsorbed to the modified electrode. Finally, negatively charged antibody-coated gold nanoparticles were attached to the surface to form the ECL immunosensor. In the presence of hIgG, hIgG was captured by its antibody. In addition, an ECL signal was detected in the presence of H 2 O 2 when a double potential was applied. The ECL immunosensor for the determination of hIgG showed a linear range of 1.0×10 13 -1.0×10 8 g/mL with a detection limit of 5.0×10 14 g/mL. This immunosensor has high sensitivity, wide linearity and good reproducibility. The superior sensitivity of the proposed ECL immunoassay mainly derives from the incorporation of ABEI-GC, which not only improves the ECL intensity, response speed, and stability, but also provides a large specific surface for high levels of protein loading. This work reveals that ABEI-GC is good nano-interface for the construction of ECL biosensors. Our strategy is promising for protein detection and may open up a new avenue for ultrasensitive label-free immunoassays. N-(aminobutyl)-N-(ethylisoluminol) (ABEI), graphene, electrochemiluminescence immunosensor
Output: SCIENCE CHINA Chemistry Ultrasensitive label-free electrochemiluminescence immunosensor based on N-(4-aminobutyl)-N-ethylisoluminol-functionalized graphene composite
To date, only influenza and RSV testing are recommended for respiratory viruses' detection in paediatric units. In this study, we described, according to seasons, ages and clinical units, the results obtained in children (<15 years old) by multiplex-PCR (mPCR) tests allowing a quick and wide range detection of all respiratory viruses. These results were also compared with RSV specific detection. All nasopharyngeal mPCR and RSV tests requested by clinicians in our French teaching hospitals group between 2011 and 2014 were retrospectively included. All repeated samples for the same children in the same month were discarded. Of the 381 mPCR tests (344 children) performed, 51.4% were positive. Positivity and viral co-infection rates were higher in the 6-36 months old strata (81% and 25%, p<0.0001 and p = 0.04, respectively). Viral distribution showed strong variations across ages. During specific influenza epidemic periods, only 1/39 (2.5%) mPCR tests were positive for influenza and 19/39 (48.7%) for other viruses. During specific RSV epidemic periods, only 8/46 (17.4%) mPCR tests were positive for RSV and 14/46 (30.4%) for other viruses. 477/1529 (31.2%) of RSV immunochromatography-tests were positive. Among the negatives PLOS ONE |
Output: Usefulness of multiplex PCR methods and respiratory viruses' distribution in children below 15 years old according to age, seasons and clinical units in France: A 3 years retrospective study
The widespread threat of severe acute respiratory syndrome (SARS) to human life has spawned challenges to develop fast and accurate analytical methods for its early diagnosis and to create a safe antiviral vaccine for preventive use. Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Methods: We synthesized 41 peptides ranging in size from 16 to 25 amino acid residues of relatively high hydrophilicity. The immunoreactivities of the peptides with SARS patient sera were determined by ELISA. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. Notably, N371 and N385, located at the COOH terminus of the N protein, inhibited binding of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of samples from SARS study patients. N385 had the highest affinity for forming peptide-antibody complexes with SARS serum. Conclusions: Five peptides from SARS structural proteins, especially two from the COOH terminus of the N protein, appear to be highly immunogenic and may be useful for serologic assays. The identification of these antigenic peptides contributes to the understanding of the immunogenicity and persistence of SARS coronavirus.
Output: Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus
A systemic disease of domestic ferrets characterized by pyogranulomatous inflammation was first recognized in Europe and the United States in 2002. The disease closely resembled feline infectious peritonitis and subsequently has been shown to be associated with ferret systemic coronavirus (FRSCV). A definitive laboratory diagnosis of this disease is typically based on a combination of immunohistochemistry (IHC) and reverse-transcriptase polymerase chain reaction tests to detect FRSCV in granulomatous lesions. In 2010, this feline infectious peritonitis-like disease was first identified in a laboratory ferret in Japan, and laboratory confirmation of the clinical diagnosis was limited to IHC. This report describes 2 cases of systemic coronavirus-associated disease in ferrets presented to Japanese veterinary hospitals. Both presented with pyogranulomatous inflammation in the abdominal cavity, and both cases tested positive for coronavirus antigen by IHC. In 1 case, for which unfixed tissues were available, FRSCV RNA was detected by reverse-transcriptase polymerase chain reaction in the affected tissues.
Output: AEMV FORUM TWO CASES OF SYSTEMIC CORONAVIRUS- ASSOCIATED DISEASE RESEMBLING FELINE INFECTIOUS PERITONITIS IN DOMESTIC FERRETS IN JAPAN
For occupational safety, healthcare workers must select and wear appropriate personal protective equipment (PPE), protective clothing, and masks as countermeasures against exposure to infectious body fluids and blood splash. It is important for healthcare workers to ensure the protective performance of each PPE against penetration of pathogens. The International Standards Organization (ISO) 22609 test evaluates the effectiveness of medical facemasks to protect against penetration of splashed synthetic blood. However, in this method, the protective performance is determined only visually, without quantification of leaked liquid volume. Therefore, in this study, we modified the ISO 22609 test method to quantify the volume of leaked liquid and obtain a more accurate assessment of the protection performance. We tested non-woven and woven materials used for masks or protective clothing, and the performance of each material was classified using this new method. We found that the quantity of leaked synthetic blood was dependent on the structural characteristics of each material. These findings will allow healthcare workers to select the most appropriate PPE for a given situation or task.
Output: PROTECTION PERFORMANCE OF BIOLOGICAL PPE 521 Performance of materials used for biological personal protective equipment against blood splash penetration
Quinine was first recognized as a potent antimalarial agent hundreds of years ago. Since then, the beneficial effects of quinine and its more advanced synthetic forms, chloroquine and hydroxychloroquine, have been increasingly recognized in a myriad of other diseases in addition to malaria. In recent years, antimalarials were shown to have various immunomodulatory effects, and currently have an established role in the management of rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, skin diseases, and in the treatment of chronic Q fever. Lately, additional metabolic, cardiovascular, antithrombotic, and antineoplastic effects of antimalarials were shown. In this review, we discuss the known various immunomodulatory mechanisms of antimalarials and the current evidence for their beneficial effects in various diseases and in potential novel applications.
Output: Hydroxychloroquine: From Malaria to Autoimmunity
There is an increasing recognition that detailed nucleic acid sequence information will be useful and even required in the diagnosis, treatment and surveillance of many significant pathogens. Because generating detailed information about pathogens leads to significantly larger amounts of data, it is necessary to develop automated analysis methods to reduce analysis time and to standardize identification criteria. This is especially important for multiple pathogen assays designed to reduce assay time and costs. In this paper, we present a successful algorithm for detecting pathogens and reporting the maximum level of detail possible using multipathogen resequencing microarrays. The algorithm filters the sequence of base calls from the microarray and finds entries in genetic databases that most closely match. Taxonomic databases are then used to relate these entries to each other so that the microorganism can be identified. Although developed using a resequencing microarray, the approach is applicable to any assay method that produces base call sequence information. The success and continued development of this approach means that a non-expert can now perform unassisted analysis of the results obtained from partial sequence data.
Output: Automated identification of multiple micro-organisms from resequencing DNA microarrays
Recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of 'recoded' genes lags far behind annotation of 'standard' genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression-a factor of approximately three increase over the previous version of the database. Recode-2 is available at
Output: Recode-2: new design, new search tools, and many more genes
Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI) networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of ''biologically central (BC)'' genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drugtargeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network. To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC) role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs) in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its ''spine'' that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.
Output: Dominating Biological Networks
Throughout history, human kind has won many battles against deadly diseases, including small pox, polio, tuberculosis and more recently severe acute respiratory syndrome. All of these diseases were defeated by prevention. Achieving cancer prevention is a global priority, but history tells us that the pathway to achievement is difficult and full of detours and roadblocks. Epidemiology and clinical evidence clearly indicate that specific factors are associated with an increased risk for cancer development. What can we learn from the past that is applicable to the reality of successful cancer prevention?
Output: Cancer Prevention Research-Then and Now
19 20 21 22 112 While we are pressed with immediacy of the COVID-19 pandemic, we also need to keep a long-term 113 view for the future of our specialty. The COVID-19 pandemic has impacted all parts of the world. Given 114 the recent history of other epidemics (for example SARS, H1N1, ebola, and MERS), it is unlikely that this 115 will be the last epidemic/pandemic crisis. This type of crisis requires allergy divisions and training 116 programs communicate by virtual global assemblies. Communication between program directors and 117 fellows across different programs can provide support and solutions, which can be adapted at each 118 division based on their needs and resources. The entire specialty should unite with the societies such as
Output: Journal Pre-proof Running a virtual allergy division and training program in the time of COVID-19 pandemic