niryuu/sni-each-converted huggingface dataset:
Background: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development. Results: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target proteincoding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the "plant-pathogen interaction" and "plant hormone signaling" pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a). Conclusion: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE.
Output: Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour
Rev DDX3 DDX5 RNA helicase RNA export a b s t r a c t RNA helicase plays an important role in host mRNA and viral mRNA transcription, transport, and translation. Many viruses utilize RNA helicases in their life cycle, while human immunodeficiency virus type 1 (HIV-1) does not encode an RNA helicase. Thus, host RNA helicase has been involved in HIV-1 replication. Indeed, DDX1 and DDX3 DEAD-box RNA helicases are known to be required for efficient HIV-1 Revdependent RNA export. However, it remains unclear whether distinct DDX RNA helicases cross-talk and cooperate to modulate the HIV-1 Rev function. In this study, we noticed that distinct DDX RNA helicases, including DDX1, DDX3, DDX5, DDX17, DDX21, DDX56, except DDX6, bound to the Rev protein and they colocalized with Rev in nucleolus or nucleus. In this context, these DEAD-box RNA helicases except DDX6 markedly enhanced the HIV-1 Rev-dependent RNA export. Furthermore, DDX3 interacted with DDX5 and synergistically enhanced the Rev function. As well, combination of other distinct DDX RNA helicases cooperated to stimulate the Rev function. Altogether, these results suggest that distinct DDX DEAD-box RNA helicases cooperate to modulate the HIV-1 Rev function. Crown
Output: Distinct DDX DEAD-box RNA helicases cooperate to modulate the HIV-1 Rev function
Objectives: The aim of this study was to assess the effect of commercial aurintricarboxylic acid (ATA) against Cryptosporidium parvum. Methods: The anticryptosporidial effect of ATA was evaluated in vitro using cell culture and double fluorogenic staining, and in vivo in experimentally infected neonatal C57BL/6 mice. Mice were orally treated for 9 consecutive days starting on the day of infection with daily ATA doses of 50 and 100 mmol/kg. Paromomycin (100 mg/kg) was used as a positive control. Results: In both in vitro models, ATA at concentrations of 100 and 10 mmol/L completely inhibited sporozoites within 10 and 60 min, respectively. Viability of oocysts exposed to 100 mmol/L and assessed by flow cytometry and in cell culture was reduced by 65% and 61%, respectively. The treatment of neonatal mice with a daily ATA dose of 100 mmol/kg led to 97-99% inhibition of infection without any observable negative effects on the animals. In comparison, the mean reduction of infection for paromomycin was 79-84%. Conclusions: ATA exerted high anticryptosporidial activity and should be considered for further study.
Output: In vitro and in vivo activity of aurintricarboxylic acid preparations against Cryptosporidium parvum
Panax ginseng Meyer, belonging to the genus Panax of the family Araliaceae, is known for its human immune system-related effects, such as immune-boosting effects. Ginseng polysaccharides (GPs) are the responsible ingredient of ginseng in immunomodulation, and are classified as acidic and neutral GPs. Although GPs participate in various immune reactions including the stimulation of immune cells and production of cytokines, the precise function of GPs together with its potential receptor(s) and their signal transduction pathways have remained largely unknown. Animal lectins are carbohydrate-binding proteins that are highly specific for sugar moieties. Among many different biological functions in vivo, animal lectins especially play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens or that are inaccessible on host cells. This review summarizes the immunological activities of GPs and the diverse roles of animal lectins in the immune system, suggesting the possibility of animal lectins as the potential receptor candidates of GPs and giving insights into the development of GPs as therapeutic biomaterials for many immunological diseases.
Output: Animal lectins: potential receptors for ginseng polysaccharides-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Objectives: The risk of acquisition and transmission of respiratory infections is high among attendees of mass gatherings (MGs). Currently used interventions have limitations yet the role of facemask in preventing those infections at MG has not been systematically reviewed. We have conducted a systematic review to synthesise evidence about the uptake and effectiveness of facemask against respiratory infections in MGs. Methods: A comprehensive literature search was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using major electronic databases such as, Medline, EMBASE, SCOPUS and CINAHL. Results: Of 25 studies included, the pooled sample size was 12710 participants from 55 countries aged 11 to 89 years, 37% were female. The overall uptake of facemask ranged from 0.02% to 92.8% with an average of about 50%. Only 13 studies examined the effectiveness of facemask, and their pooled estimate revealed significant protectiveness against respiratory infections (relative risk [RR] = 0.89, 95% CI: 0.84-0.94, p < 0.01), but the study end points varied widely. Conclusion: A modest proportion of attendees of MGs use facemask, the practice is more widespread among health care workers. Facemask use seems to be beneficial against certain respiratory infections at MGs but its effectiveness against specific infection remains unproven.
Output: Uptake and effectiveness of facemask against respiratory infections at mass gatherings: a systematic review
For gene delivery to the lung, the challenges are high, but successful treatment of cystic fibrosis or achieving immunity against the global infectious diseases provide an allure that cannot be ignored. This chapter summarizes and reviews nonviral DNA delivery for both gene therapy and DNA vaccination in the lung. Aerosolization of DNA is evaluated, and the stability during this process is discussed. Carriers for DNA are then discussed including lipoplexes and polyplexes, with a particular focus on systems that achieve good transfection and minimize potential toxicity. Then principles of DNA vaccination are introduced, and the advantages of pulmonary vaccination are discussed. Finally, the transport of plasmid DNA vaccines into the lungs is reviewed.
Output: Pulmonary Delivery of Plasmid DNA for Disease Prevention and Therapy
Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O 1 BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.
Output: Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom
The interaction with lipids of a synthetic peptide corresponding to the transmembrane domain of influenza hemagglutinin was investigated by means of electron spin resonance. A detailed analysis of the electron spin resonance spectra from spin-labeled phospholipids revealed that the major effect of the peptide on the dynamic membrane structure is to induce highly ordered membrane domains that are associated with electrostatic interactions between the peptide and negatively charged lipids. Two highly conserved residues in the peptide were identified as being important for the membrane ordering effect. Aggregation of large unilamellar vesicles induced by the peptide was also found to be correlated with the membrane ordering effect of the peptide, indicating that an increase in membrane ordering, i.e., membrane dehydration, is important for vesicle aggregation. The possibility that hydrophobic interaction between the highly ordered membrane domains plays a role in vesicle aggregation and viral fusion is discussed.
Output: Two Conserved Residues Are Important for Inducing Highly Ordered Membrane Domains by the Transmembrane Domain of Influenza Hemagglutinin
Most studies exploring the role of upper airway viruses and bacteria in paediatric acute respiratory infections (ARI) focus on specific clinical diagnoses and/or do not account for virus-bacteria interactions. We aimed to describe the frequency and predictors of virus and bacteria codetection in children with ARI and cough, irrespective of clinical diagnosis. Bilateral nasal swabs, demographic, clinical and risk factor data were collected at enrollment in children aged <15 years presenting to an emergency department with an ARI and where cough was a symptom. Swabs were tested by polymerase chain reaction for 17 respiratory viruses and seven respiratory bacteria. Logistic regression was used to investigate associations between child characteristics and codetection of the organisms of interest. Between December 2011 and August 2014, swabs were collected from 817 (93.3%) of 876 enrolled children, median age 27.7 months (interquartile range 13.9-60.3 months). Overall, 740 (90.6%) of 817 specimens were positive for any organism. Both viruses and bacteria were detected in 423 specimens (51.8%). Factors associated with codetection were age (adjusted odds ratio (aOR) for age <12 months = 4.9, 95% confidence interval (CI) 3.0, 7.9; age 12 to <24 months = 6.0, 95% CI 3.7, 9.8; age 24 to <60 months = 2.4, 95% CI 1.5, 3.9), male gender (aOR 1.46; 95% CI 1.1, 2.0), child care attendance (aOR 2.0; 95% CI 1.4, 2.8) and winter enrollment (aOR 2.0; 95% CI 1.3, 3.0). Haemophilus influenzae dominated the virus-bacteria pairs. Virus-H. influenzae interactions in ARI should be investigated further, especially as the contribution of nontypeable H. influenzae to acute and chronic respiratory diseases is being increasingly recognized.
Output: Prevalence, codetection and seasonal distribution of upper airway viruses and bacteria in children with acute respiratory illnesses with cough as a symptom
Background: Clinical competency certifications are important parts of internal medicine residency training. This study aims to evaluate a composite objective structured clinical examination (OSCE) that assesses postgraduate year-1 (PGY 1 ) residents' acquisition of the six core competencies defined by the Accreditation council for Graduate Medical Education (ACGME). Methods: Six-core-competency-based OSCE was used as examination of the clinical performance of 192 PGY 1 residents during their 3-month internal medicine training between 2007 January and 2009 December. For each year, the reliability of the entire examination was calculated with Cronbach's alpha. Results: The reliability of six-core-competency-based OSCE was acceptable, ranging from 0.69 to 0.87 between 2007 and 2009. In comparison with baseline scores, the summary scores and core-competency subscores all showed significant increase after PGY 1 residents finished their 3-month internal medicine training program. Conclusion: By using a structured development process, the authors were able to create reliable evaluation items for determining PGY 1 residents' acquisition of the ACGME core competencies.
Output: Original Article
Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.
Output: Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery
In this study, we isolated and characterized an insect nidovirus from the mosquito Culex tritaeniorhynchus Giles (Diptera: Culicidae) in Vietnam, as an additional member of the new family Mesoniviridae in the order Nidovirales. The virus, designated ''Dak Nong virus (DKNV),'' shared many characteristics with Cavally virus and Nam Dinh virus, which have also been discovered recently in mosquitoes, and these viruses should be considered members of a single virus species, Alphamesonivirus 1. DKNV grew in cultured mosquito cells but could not replicate in the cultured vertebrate cells tested. N-terminal sequencing of the DKNV structural proteins revealed two posttranslational cleavage sites in the spike glycoprotein precursor. DKNV is assumed to be a new member of the species Alphamesonivirus 1, and the current study provides further understanding of viruses belonging to the new family Mesoniviridae. R. Kuwata and T. Satho contributed equally.
Output: Characterization of Dak Nong virus, an insect nidovirus isolated from Culex mosquitoes in Vietnam
Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity. To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (�20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.
Output: The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea
The performance of a recently developed real-time PCR system, the ExiStation HBV diagnostic system, for quantitation of hepatitis B virus (HBV) in human blood was evaluated. The detection limit, reproducibility, cross-reactivity, and interference were evaluated as measures of analytical performance. For the comparison study, 100 HBV-positive blood samples and 100 HBV-negative samples from Korean Blood Bank Serum were used, and the results of the ExiStation HBV system showed good correlation with those obtained using the Cobas TaqMan (r 2 = 0.9931) and Abbott real-time PCR systems (r 2 = 0.9894). The lower limit of detection was measured as 9.55 IU/mL using WHO standards and the dynamic range was linear from 6.68 to 6.68 × 10 9 IU/mL using cloned plasmids. The within-run coefficient of variation (CV) was 9.4%, 2.1%, and 1.1%, and the total CV was 11.8%, 3.6%, and 1.7% at a concentration of 1.92 log 10 IU/mL, 3.88 log 10 IU/mL, and 6.84 log 10 IU/mL, respectively. No cross-reactivity or interference was detected. The ExiStation HBV diagnostic system showed satisfactory analytical sensitivity, excellent reproducibility, no cross-reactivity, no interference, and high agreement with the Cobas TaqMan and Abbott real-time PCR systems, and is therefore a useful tool for the detection and monitoring of HBV infection.
Output: Performance evaluation of ExiStation HBV diagnostic system for hepatitis B virus DNA quantitation
Rapid diagnosis of respiratory virus infections contributes to patient care. This systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. We searched Medline and EMBASE for studies evaluating these tests against polymerase chain reaction as the reference standard. Of 179 studies included, 134 evaluated rapid tests for influenza viruses, 32 for respiratory syncytial virus (RSV), and 13 for other respiratory viruses. We used the bivariate random effects model for quantitative meta-analysis of the results. Most tests detected only influenza viruses or RSV. Summary sensitivity and specificity estimates of tests for influenza were 61.1% and 98.9%. For RSV, summary sensitivity was 75.3%, and specificity, 98.7%. We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Because of incomplete reporting, the risk of bias was often unclear. Despite their intended use at the point of care, 26.3% of tests were evaluated in a laboratory setting. Although newly developed tests seem more sensitive, high-quality evaluations of these tests are lacking.
Output: Clinical Infectious Diseases Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis
Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction. Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell. In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells. This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection. Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in ad- vance of infection. As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection. These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis. IMPORTANCE Citation Schmidt N, Hennig T, Serwa RA, Marchetti M, O'Hare P. 2015. Remote activation of host cell DNA synthesis in uninfected cells signaled by infected cells in advance of virus transmission.
Output: Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission
Background: During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach. Methods: 33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness. Results: Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere. Conclusions: Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.
Output: Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct
Background: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR), transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website
Output: Coronavirus 3CL pro proteinase cleavage sites: Possible relevance to SARS virus pathology
Respiratory viral infections are often implicated as triggers of chronic rhinosinusitis (CRS) flare-ups. However, there is a paucity of respiratory viral surveillance studies in CRS patients, and such studies could elucidate the potential role of viruses in promoting symptoms and aggravating mucosal inflammation. Therefore, a prospective case-control study was conducted to determine the prevalence of respiratory viruses in CRS patients and non-CRS controls. Nasal lavage fluids and turbinate epithelial cells were collected prospectively from 111 CRS patients and 50 controls. Multiplex PCR was used to identify common respiratory viruses in both sample types and the infection rate was compared between groups. Respiratory viruses were detected in 50.5% of lavage samples and in 64.0% of scraping samples from CRS patients. The overall infection rate was significantly different in CRS patients and controls (odds ratio, 2.9 in lavage and 4.1 in scraping samples). Multiple viral infections were detected more frequently in lavage samples from CRS patients than those from controls (P < 0.01; odds ratio, 7.7). Rhinovirus was the most prevalent virus and the only virus with a significantly different infection rate in CRS patients and controls in both samples (odds ratio, 3.2 in lavage and 3.4 in scraping samples). This study detected a higher prevalence of respiratory viruses in CRS patients than controls, suggesting that there may be significant associations between inflammation of CRS and respiratory viruses, particularly rhinovirus. Further studies should investigate the exact role of highly prevalent respiratory viruses in CRS patients during symptomatic aggravation and ongoing mucosal inflammation.
Output: High Rates of Detection of Respiratory Viruses in the Nasal Washes and Mucosae of Patients with Chronic Rhinosinusitis
Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK's upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.
Output: Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
Expected risk of infection from patients to healthcare workers in an AIIR was found. • We investigated how to remove airborne contamination effectively in AIIRs. • Both full-scale field experiments and CFD simulations were performed. • Transport of gaseous pollutants is indicated by tracer gas. • By changing the exhaust air flow, the exposure pollutant level was significantly reduced. This study, that is practice-based learning in a real hospital construction project, has evaluated the ventilation performance of three strategies in the protection of health care workers and HVAC control for airborne infectious diseases induced by contaminated exhaled air from patients in a negative pressure isolation room. This paper examines air flow path and airborne pollutant distribution by computational fluid dynamics modeling and field measurement. In hospitals, the risk of virus diffusion mainly depends on air flow behavior and changes in direction caused by supply air and exhaust air locations. An improved isolation room ventilation strategy has been suggested, and is found to be the most efficient in removing contaminants based on the observations and simulation results from three ventilation systems. The results show that ventilation systems utilizing the "lowlevel extraction" technique are very effective at removing pollutants in the human breathing zone. A new clean isolation room ventilation strategy has been developed that employs two exhaust air grilles on the wall behind the bed at low floor level, coupled with a fan filter unit, and is found to have the highest pollutant removal efficiency.
Output: Investigation on the contaminant distribution with improved ventilation system in hospital isolation rooms: Effect of supply and exhaust air diffuser configurations
Highly infectious diseases can spread rapidly across borders through travel or trade, and international coordination is essential to a prompt and efficient response by public health laboratories. Therefore, developing strategies to identify priorities for a rational allocation of resources for research and surveillance has been the focus of a large body of research in recent years. This paper describes the activities and the strategy used by a European-wide consortium funded by the European Commission, named EMERGE (Efficient response to highly dangerous and emerging pathogens at EU level), for the selection of high-threat pathogens with cross-border potential that will become the focus of its preparedness activities. The approach used is based on an objective scoring system, a close collaboration with other networks dealing with highly infection diseases, and a diagnostic gaps analysis. The result is a tool that is simple, objective and adaptable, which will be used periodically to re-evaluate activities and priorities, representing a step forward towards a better response to infectious disease emergencies.
Output: Prioritization of High Consequence Viruses to Improve European Laboratory Preparedness for Cross-Border Health Threats
To investigate canine kobuvirus (CaKoV) infection, fecal samples (n = 59) were collected from dogs with or without diarrhea (n = 21 and 38, respectively) in the Republic of Korea (ROK) in 2012. CaKoV infection was detected in four diarrheic samples (19.0 %) and five non-diarrheic samples (13.2 %). All CaKoV-positive dogs with diarrhea were found to be infected in mixed infections with canine distemper virus and canine parvovirus or canine adenovirus. There was no significant difference in the prevalence of CaKoV in dogs with and without diarrhea. By phylogenetic analysis based on partial 3D genes and complete genome sequences, the Korean isolates were found to be closely related to each other regardless of whether they were associated with diarrhea, and to the canine kobuviruses identified in the USA and UK. This study supports the conclusion that CaKoVs from different countries are not restricted geographically and belong to a single lineage.
Output: Canine kobuvirus infections in Korean dogs
Crimean Congo hemorrhagic fever virus (CCHFV) causes an acute disease with the potential of a fatal outcome. The virus is prevalent in about 30 countries. Clinical symptoms of infection commonly include fever, myalgia, and hemorrhages. Levels of liver enzymes are raised, and bleeding markers are often increased. A role of inflammatory cytokines in the pathogenesis has been suggested, and CCHFV employs a range of passive and active mechanisms to avoid induction of the antiviral type I interferons. Here, we review the most recent findings on the molecular pathogenesis and the interaction of CCHFV with the type I interferon and cytokine responses and discuss implications for pathogenesis. #
Output: Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis
Influenza A virus (IAV) is a major cause of respiratory illness. Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious "universal" IAV vaccination strategies. Recent studies have highlighted that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters. Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections. Herein, we report on an intranasally administered biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax) capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations. Our findings also demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs, both systemic and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4 and CD8 T cells. Altogether our findings show that an intranasally administered nanovaccine can induce immunity within the lungs, similar to what occurs during IAV infections, and thus could prove useful as a strategy for providing "universal" protection against IAV.
Output: a section of the journal Frontiers in Immunology Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and Confers Protection Against Homologous and Heterologous Influenza A Virus Infections
Viral encephalomyelitis is caused by virus infections of neurons in the brain and spinal cord. Recovery is dependent on immune-mediated control and clearance of virus from these terminally differentiated essential cells. Preservation of neuronal function is essential for prevention of neurologic sequelae such as paralysis, seizures and cognitive deficits. Using the model system of Sindbis virus-induced encephalomyelitis in mice, we have shown that immune-mediated clearance of infectious virus from neurons is a noncytolytic process. The major effectors are antibody to the E2 surface glycoprotein produced by B cells, and interferon-γ produced by T cells. These effectors work in synergy, but neuronal populations differ in their responses to each. Virus is least likely to be cleared from brain neurons and most likely to be cleared from motor neurons in the cervical and thoracic regions of the spinal cord. Because the infected neurons are not eliminated, viral RNA persists and long-term control is needed to prevent virus reactivation. Virus-specific antibodysecreting cells residing in the nervous system after recovery from infection are likely to be important for long-term control.
Output: Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons
Advanced techniques in the fi eld of diagnostic microbiology have made amazing progress over the past two decades due largely to a technological revolution in the molecular aspects of microbiology [ 1, 2 ] . In particular, rapid molecular methods for nucleic acid ampli fi cation and characterization combined with automation and userfriendly software have signi fi cantly broadened the diagnostic capabilities of modern clinical microbiology laboratories. Molecular methods such as nucleic acid ampli fi cation tests (NAATs) rapidly are being developed and introduced in the clinical laboratory setting. Indeed, every section of the clinical microbiology laboratory, including bacteriology, mycology, mycobacteriology, parasitology, and virology, have bene fi ted from these advanced techniques. Because of the rapid development and adaptation of these molecular techniques, the interpretation and relevance of the results produced by such molecular methods has lagged somewhat behind. The purpose of this chapter is to review and discuss the interpretation and relevance of results produced by these advanced molecular techniques. Moreover, this chapter will address the "myths" of NAATs, as these myths can markedly in fl uence the interpretation and relevance of these results.
Output: Interpretation and Relevance of Advanced Technique Results
Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.
Output: Factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control
Bernard, S., Bottreau, E., Aynaud, J.M., Have, P. and Szymansky, J., 1989. Natural infection with the porcine respiratory coronavirus induces protective lactogenic immunity against transmissible gastroenteritis. Vet. Microbiol., 21: 1-8. Our objective was to evaluate the level of passive protection against transmissible gastroenteritis (TGE) among 57 newborn piglets nursing from seven seropositive sows previously naturally infected with porcine respiratory coronavirus (PRCV). After challenge exposure we observed mortality rates of 44% for litters of seven PRCV-infected sows, 40% for litters of four sows orally immunized with the attenuated TGEV strain Nouzilly, and 91% for litters of seven seronegative susceptible sows. A blocking ELISA with two appropriate monoclonal antibodies distinguished serological responses of PRCV-infected sows from those of TGEV-immunized sows. The results suggest that natural infection of the sow with PRCV may induce a degree of protective lactogenic immunity against TGE.
Output: Natural Infection with the Porcine Respiratory Coronavirus Induces Protective Lactogenic Immunity against Transmissible Gastroenteritis
The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC-I 13 molecules require the assembly of a peptide-MHC-I-β2m (aka pMHC-I) trimolecular complex 14 for TCR recognition, which is the critical activation link for triggering antiviral T cell immunity. 15 Ursidae includes 5 genera and 8 species; however, research on T cell immunology in this family, 16 especially structural immunology, is lacking. In this study, the structure of the key trimolecular 17 complex pMHC-1 (aka pAime-128), which binds a peptide from canine distemper virus, was solved 18 for the first time using giant panda as a representative species of Ursidae. The structural 19 characteristics of the giant panda pMHC-I complex, including the unique pockets in the 20 peptide-binding groove (PBG), were analyzed in detail. Comparing the panda pMHC-I to others 21 in the bear family and extending the comparison to other mammals revealed distinct features. 22 Spriggs H, Dear PH, Briggs AW. 2008. Mitochondrial genomes reveal an explosive radiation 469 of extinct and extant bears near the Miocene-Pliocene boundary. Bmc Evolutionary Biology 470 8:220-220. 471 22. et al. 2009. The sequence and de novo assembly of the 476 giant panda genome. Nature 463:311. 477 Pan HJ, Wan QH, Fang SG. 2008. Molecular characterization of major histocompatibility 478 complex class I genes from the giant panda (Ailuropoda melanoleuca). Immunogenetics
Output: Crystal structure of the giant panda MHC class I complex: first insights into the viral 1 peptide presentation profile in the bear family 2
The newborn calf's gastrointestinal tract is sterile at birth, but by 3 days of age coliforms, Lactobacilli, and Bifidobacteria are the predominant flora in the feces. During the preweaning period, calves are susceptible to diarrhea that can lead to high levels of morbidity and mortality. Diarrhea has been related with a decrease of beneficial microbiota and an increase of coliform counts in feces. Prebiotic supplements are believed to decrease diarrhea and positively affect some parameters of the immune system. In calves, these supplements have shown some promising effects on intestinal microbial populations but there is limited information about effects on immunity. The main objectives of this study were to evaluate effects of a prebiotic supplement containing fermentation products of lactic acid bacteria on the mucosal immune system by measuring fecal and salivary IgA and to evaluate calf health and growth performance. In this trial 40 Holstein calves were randomly assigned to receive milk replacer with a prebiotic supplement (20 g/day Prebio Support™; Meiji Feed Co., Ltd. Tokyo, Japan) or the same milk replacer with no prebiotic (control). Fecal and salivary IgA, calf health, plasma IgG, and lymphocyte counts were not affected by treatment. Lactobacilli count in feces was higher (P = 0.05) and Bifidobacteria tended to be higher (P = 0.07) in calves fed prebiotic. Prebiotic supplement increased beneficial bacteria in calves, but did not decrease overall incidence of diarrhea in this trial. Calves in this study were all affected by cryptosporidiosis and some were treated with antibiotics, so it is possible that this limited some of the effects of the prebiotic product. Fecal IgA seemed to be a good measure of mucosal immunity, and more studies are needed to develop methods to measure this type of immunity in calves.
Output: The effects of a prebiotic supplement (Prebio Support) on fecal and salivary IgA in neonatal dairy calves
Sensors and biosensors have been increasingly used for clinical analysis due to their miniaturization and portability, allowing the construction of diagnostic devices for point-of-care testing. This paper presents an up-to-date overview and comparison of the analytical performance of sensors and biosensors recently used in clinical analysis. This includes cancer and cardiac biomarkers, hormones, biomolecules, neurotransmitters, bacteria, virus and cancer cells, along with related significant advances since 2011. Some methods of enhancing the analytical performance of sensors and biosensors through their figures of merit are also discussed.
Output: Critical overview on the application of sensors and biosensors for clinical analysis
Caliciviruses are important human and animal pathogens. Novel caliciviruses have been identified recently in dogs, raising questions about their pathogenic role and concerns regarding their zoonotic potential. By screening stool samples of young or juvenile dogs using RT-PCR assays, sapoviruses (SaVs) were found in 7/320 (2.2%) samples of animals with acute gastroenteritis while they were not detected in healthy animals (0/119). The sequence of a nearly 3 kb portion at the 3′ end of the genome, encompassing the RNA-dependent RNA polymerase (RdRp), the capsid region (ORF1) and the ORF2 were determined for three strains. A distinctive genetic feature in canine SaVs was a 4-nucleotide (nt) interval between the ORF1 and ORF2. Two strains (Bari/4076/ 07/ITA and Bari/253/07/ITA) were very closely related in the RdRp and capsid regions to the strain AN210D/ 09/USA (90.4-93.9% nt), while strain Bari/5020/07/ITA displayed only 71.0-72.0% nt identity to this group of canine SaVs and 76.0% to strain AN196/09/USA. Overall, these findings indicate that the canine SaVs detected in Italy may represent distinct capsid types, although all currently known SaVs segregate into the novel proposed genogroup, tentatively named as GXIII.
Output: Detection and molecular characterization of sapoviruses in dogs
The seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early-warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real-time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high-dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early-warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early-warning signal, with an average of 4week window lead prior to each seasonal outbreak of influenza, was provided by DNM-based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level. city network, critical transition, dynamic network biomarker (DNB), dynamic network marker (DNM), early-warning signal, influenza outbreak
Output: Detecting early-warning signals of influenza outbreak based on dynamic network marker