niryuu/sni-each-converted huggingface dataset:
The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. Methods: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption Results: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. Conclusion: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.
Output: BMC Infectious Diseases Initial psychological responses to Influenza A, H1N1 ("Swine flu")
Background: Porcine epidemic diarrhea virus (PEDV) is emerging as a pathogenic coronavirus that causes a huge economic burden to the swine industry. Interaction of the viral spike (S) surface glycoprotein with the host cell receptor is recognized as the first step of infection and is the main determinant of virus tropism. The mechanisms by which neutralizing antibodies inhibit PEDV have not been defined. Isolating PEDV neutralizing antibodies are crucial to identifying the receptor-binding domains of the viral spike and elucidating the mechanism of protection against PEDV infection. Methods: B cell hybridoma technique was used to generate hybridoma cells that secrete specific antibodies. E.coli prokaryotic expression system and Bac-to-Bac expression system were used to identify the target protein of each monoclonal antibody. qPCR was performed to analyze PEDV binding to Vero E6 cells with neutralizing antibody. Results: We identified 10 monoclonal antibodies using hybridoma technology. Remarkably, 4 mAbs (designed 2G8, 2B11, 3D9, 1E3) neutralized virus infection potently, of which 2B11 and 1E3 targeted the conformational epitope of the PEDV S protein. qPCR results showed that both 2B11 and 2G8 blocked virus entry into Vero cells. Conclusion: The data suggested that PEDV neutralizing antibody inhibited virus infection by binding to infectious virions, which could work as a tool to find the receptor-binding domains.
Output: Neutralizing antibodies against porcine epidemic diarrhea virus block virus attachment and internalization
Background: Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential to direct therapy of acute graft dysfunction and identify epidemic trends. Traditional techniques of serology and viral culture are limited by the lack of antibody response and delay in diagnosis. We examined the clinical utility of indirect fluorescent antibody (IFA) testing in adult lung transplant patients with suspected RVI, compared with serology and culture. Nasopharyngeal and throat swabs (NT) were obtained to sample epithelial cells, followed by application of monoclonal antibody to respiratory syncytial virus, adenovirus, parainfluenza 1-3 and influenza A and B. The Bartels Respiratory Viral Detection kit was used with IFA results available within 24 hours. : Nine of 18 patients tested positive for RVI with influenza A (n ϭ 8) and influenza B (n ϭ 1) detected. The sensitivity of IFA (67%) was higher than that of cell culture (45%). With intensive supportive therapy, infection was self-limiting in bronchiolitis obliterans syndrome (BOS) Grade 0 -2 patients. However, patients with BOS Grade 3 manifested an acute exacerbation of airflow obstruction, which proved to be irreversible. Lung transplant patients with "flu-like" symptoms should proceed to IFA testing of NT swab specimens for early diagnosis. Samples collected within 7 days of symptom onset have high sensitivity as compared with serology and viral culture techniques. A cotton swab moistened in physiologic saline was inserted into both nostrils and gently rotated to absorb secretions from the posterior nasopharyngeal area. A second swab was used to vigorously rub the posterior oropharynx. Each swab was placed in 2 162 Hopkins et al.
Output: CLINICAL LUNG AND HEART/LUNG TRANSPLANTATION Indirect Fluorescent Antibody Testing of Nasopharyngeal Swabs for Influenza Diagnosis in Lung Transplant Recipients
Mild encephalitis/encephalopathy with reversible splenial lesion (MERS); MRI; Splenium of the corpus callosum; Child Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome that can be related to infectious and non-infectious conditions. Patients present with mild neurological symptoms, and magnetic resonance imaging typically demonstrate a reversible lesion with transiently reduced diffusion in the splenium of the corpus callosum. Here, we describe MERS in a 10-year-old boy who presented with fever and consciousness and who completely recovered within a few days. Streptococcus pneumoniae was the causative agent. Although viruses (especially influenza A and B) are the most common pathogen of MERS, for proper management, bacteria should be considered, as they may also lead to this condition.
Output: Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) associated with Streptococcus pneumoniae Bacteraemia
A Filippov epidemic model with media coverage is proposed to describe the real characteristics of media/psychological impact in the spread of an infectious disease. We extend the existing models by incorporating a piecewise continuous transmission rate to describe that the media coverage exhibits its effect once the number of infected individuals exceeds a certain critical level. Mathematical and bifurcation analyses with regard to the local, global stability of equilibria and local sliding bifurcations are performed. Our main results show that the system stabilizes at either the equilibrium points of the two subsystems or the new endemic state induced by the on-off media effect, depending on the threshold levels. The finding suggests that a previously chosen level of the desired number of infected individuals can be reached when the threshold policy and other parameters are chosen properly.
Output: A Filippov system describing media effects on the spread of infectious diseases
An epidemiological study was carried out on farms in Galicia (NW Spain) to investigate the prevalence of and the risk factors associated with the spread of infection by Cryptosporidium parvum in calves of less than 3 weeks of age. A total of 22 cattle farms (10 beef herds and 12 dairy herds) were visited once every 21 days between January and December 2000. A faecal sample was collected directly from the rectum of each of the 844 calves born during the study period. Each sample was studied macroscopically to establish its consistency as liquid, soft or solid, and the presence of mucus or blood noted. C. parvum oocysts were identified by direct microscopic examination and the intensity of infection established semiquantitatively as slight, moderate or severe. Of the 844 calves, 404 were found to have the parasite in their faeces, i.e. the prevalence was 47.9%. Statistical analysis of the risk factors such as general characteristics of the farm and the housing conditions of the calves, revealed three variables that significantly effect the risk of cryptosporidial infection in suckling calves: the method of cleaning, the type of flooring and the frequency of cleaning.
Output: Prevalence of and risk factors involved in the spread of neonatal bovine cryptosporidiosis in Galicia (NW Spain)
Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirusinfected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60-80% and sesquiterpenes suppressed herpes virus infection by 40-98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dosedependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.
Output: Original Article Screening for Antiviral Activities of Isolated Compounds from Essential Oils
The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplantassociated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcareassociated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients.
Output: Infection Prevention in Transplantation
Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-CoV protein 6 (P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon (IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen cDNA library. KEYWORDS severe acute respiratory syndrome coronavirus (SARS-CoV); P6; N-Myc (and STAT) interactor (Nmi); interferon (IFN) signaling pathway; ubiquitination; proteosomal degradation
Output: Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc (and STAT) interactor
We investigated whether infection with a novel human coronavirus (HCoV), called "New Haven coronavirus" (HCoV-NH)-which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63-is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were enrolled in our study. Serum, peripheral-blood mononuclear cells, nasopharyngeal aspirates, throat swabs, and rectal swabs from these patients were assayed for HCoV-NL63 by real-time reverse-transcriptase (RT) polymerase chain reaction (PCR), and the throat swabs, nasopharyngeal aspirates, and rectal swabs were also assayed for HCoV-NH by RT-PCR. All PCR results were negative for both HCoV-NL63 and HCoV-NH; therefore, we did not find any association between HCoV-NH infection and KD in Taiwan. Kawasaki disease (KD) is an acute systemic febrile illness of unknown etiology that predominantly affects children !5 years old. Initially described in 1967 by Kawasaki [1], it has become the most common cause of acquired heart disease in children in the developed world, as rheumatic heart disease occurs much less frequently than before. Although normally self-limiting, KD is associated with a range of complications, the most important
Output: Lack of Association between Infection with a Novel Human Coronavirus (HCoV), HCoV-NH, and Kawasaki Disease in Taiwan
The membrane bound metalloprotease aminopeptidase N (APN, CD13, EC 3.4.11.2) is a well established marker of normal and malignant cells of the myelo-monocytic lineage. It is also expressed by leukaemic blasts of a small group of patients suffering from acute or chronic lymphoid leukaemia. Recently, the expression of the APN gene in T cell lines as well as the induction of APN gene and surface expression in human peripheral T cells by mitogenic activation have been demonstrated. Here, by means of cytofluorimetric analysis evidence is provided, that the induction of APN surface expression is partially resistent to the action of the inhibitors of protein biosynthesis, puromycin and cycloheximide, and is not prevented by tunicamycin, an inhibitor of glycosylation. These data suggest that the rapid mitogen-induced surface expression of APN, detectable 20 hours after stimulation is dominated by mechanisms not dependent on de novo protein biosynthesis or glycosylation. As shown by simultaneous analyses, the inhibitors used did also differently modify the induction of surface expression of other inducible glycosylated leukocyte surface antigens, namely CD2S, CD69 and CD9S.
Output: Rapid Mitogen-Induced Aminopeptidase N Surface Expression in Human T Cells is Dominated by Mechanisms Independent of de novo Protein Biosynthesis
Group C serogroup includes members of the Orthobunyavirus genus (family Peribunyaviridae) and comprises 15 arboviruses that can be associated with febrile illness in humans. Although previous studies described the genome characterization of Group C orthobunyavirus, there is a gap in genomic information about the other viruses in this group. Therefore, in this study, complete genomes of members of Group C serogroup were sequenced or resequenced and used for genetic characterization, as well as to understand their phylogenetic and evolutionary aspects. Thus, our study reported the genomes of three new members in Group C virus (Apeu strain BeAn848, Itaqui strain BeAn12797 and Nepuyo strain BeAn10709), as well as re-sequencing of original strains of five members: Caraparu (strain BeAn3994), Madrid (strain BT4075), Murucutu (strain BeAn974), Oriboca (strain BeAn17), and Marituba (strain BeAn15). These viruses presented a typical genomic organization related to members of the Orthobunyavirus genus. Interestingly, all viruses of this serogroup showed an open reading frame (ORF) that encodes the putative nonstructural NSs protein that precedes the nucleoprotein ORF, an unprecedented fact in Group C virus. Also, we confirmed the presence of natural reassortment events. This study expands the genomic information of Group C viruses, as well as revalidates the genomic organization of viruses that were previously reported.
Output: Revalidation and genetic characterization of new members of Group C (Orthobunyavirus genus, Peribunyaviridae family) isolated in the Americas
An association between many psychiatric and gluten-related disorders has been known for some time. In the case of schizophrenia and mood disorders, the major psychiatric disorders, there is much evidence, not without contradictions, of a possible association between schizophrenia and celiac disease. The association between mood disorders and gluten-related disorders, especially celiac disease, has only been studied for depression, often coupled with anxiety, and very recently for bipolar disorder. Since non-celiac gluten sensitivity is now known to be different from celiac disease, many studies have shown that gluten sensitivity is also associated with major psychiatric disorders. Here we review the literature on the association between schizophrenia/mood disorders and celiac disease/ gluten sensitivity, pointing out the differences between these associations.
Output: Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders
All plus-strand RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that functions as the catalytic subunit of the viral replication/transcription complex, directing viral RNA synthesis in concert with other viral proteins and, sometimes, host proteins. RNA synthesis essentially can be initiated by two different mechanisms, de novo initiation and primer-dependent initiation. Most viral RdRps have been identified solely on the basis of comparative sequence analysis, and for many viruses the mechanism of initiation is unknown. In this study, using the family prototype equine arteritis virus (EAV), we address the mechanism of initiation of RNA synthesis in arteriviruses. The RdRp domains of the members of the arterivirus family, which are part of replicase subunit nsp9, were compared to coronavirus RdRps that belong to the same order of Nidovirales, as well as to other RdRps with known initiation mechanisms and three-dimensional structures. We report here the first successful expression and purification of an arterivirus RdRp that is catalytically active in the absence of other viral or cellular proteins. The EAV nsp9/RdRp initiates RNA synthesis by a de novo mechanism on homopolymeric templates in a template-specific manner. In addition, the requirements for initiation of RNA synthesis from the 3 end of the viral genome were studied in vivo using a reverse genetics approach. These studies suggest that the 3-terminal nucleotides of the EAV genome play a critical role in viral RNA synthesis.
Output: De Novo Initiation of RNA Synthesis by the Arterivirus RNA-Dependent RNA Polymerase ᰔ Downloaded from
The chemokine CXCL10 exerts antiviral effects within the central nervous system (CNS) through the recruitment of virus-specific T cells. However, elevated levels of CXCL10 may induce neuronal apoptosis given its receptor, CXCR3, is expressed by neurons. Using a murine model of West Nile virus (WNV) encephalitis, we determined that WNV-infected neurons express TNF-α, which down-regulates neuronal CXCR3 expression via signaling through TNFR1. Downregulation of neuronal CXCR3 decreased CXCL10-mediated calcium transients and delayed Caspase 3 activation. Loss of CXCR3 activation, via CXCR3-deficiency or pretreatment with TNF-α prevented neuronal apoptosis during in vitro WNV infection. These results suggest that neuronal TNF-α expression during WNV encephalitis may be an adaptive response to diminish CXCL10-induced death.
Output: TNF-α-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis
This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at http://www.healthcybermap.org/GoogleMapsAPI/ -Google Maps API (Application Programming Interface) version, http://www.healthcybermap.org/ GoogleEarthKML/ -Google Earth KML (Keyhole Markup Language) version, and http:// www.healthcybermap.org/MSNVirtualEarth/ -MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future.
Output: Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control
We assess the impact of asymptomatic transmission on epidemic potential of novel respiratory pathogens (like COVID-19) -as measured both by the basic reproduction number (i.e., the expected number of secondary cases generated by an average primary case in a fully susceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. We show that the impact of asymptomatic transmission depends on generation intervals (i.e., time between when an individual is infected and when that individual infects another person). If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases, R 0 will be over-estimated, and if they have a longer generation interval, R 0 will be underestimated. We also show that as the length of asymptomatic generation intervals increase, estimates of the realized proportion of asymptomatic transmission during the exponential phase of the epidemic decrease. Our analysis provides a rationale for assessing the duration of asymptomatic cases of COVID-19 in addition to their prevalence in the population.
Output: The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak
Background: Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF). This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFa) axis in community-based cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy controls (n = 50). Enzyme-linked immunosorbent assays were used to investigate levels of TNFa, its two receptors (TNFR1 and TNFR2), and a non-TNFa cytokine, interleukin-6 (IL-6), in plasma derived from peripheral blood samples. Plasma levels of TNFa and TNFR1 were significantly elevated in HFPEF relative to controls, while levels of TNFR2 were significantly higher in HFPEF than both controls and HFREF. TNFa, TNFR1 and TNFR2 were each significantly associated with at least two of the following: age, estimated glomerular filtration rate, hypertension, diabetes, smoking, peripheral vascular disease or history of atrial fibrillation. TNFR2 levels were also significantly associated with increasing grade of diastolic dysfunction and severity of symptoms in HFPEF. Conclusions: Inflammation mediated through TNFa and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.
Output: Circulating Levels of Tumor Necrosis Factor-Alpha Receptor 2 Are Increased in Heart Failure with Preserved Ejection Fraction Relative to Heart Failure with Reduced Ejection Fraction: Evidence for a Divergence in Pathophysiology
Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch-and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its preclinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States.
Output: The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood
Until now, the risk of HEV infection in schizophrenia was unknown. The present results showed that the seroprevalence of anti-HEV IgG and anti-HEV IgM in schizophrenia were significantly higher than that in healthy controls. Anti-HEV IgG positivity increased with age and with the duration of disease in schizophrenia patients. Moreover, schizophrenia patients with increased CD4 ? /CD8 ? T-cell ratios ([2.03) had higher anti-HEV IgG detection rates than those with normal ratios (1.05-2.03). Compared with the schizophrenia patients who tested anti-HEV IgG negative, the levels of interleukin-4 and interleukin-10 (Th2 cytokines) were significantly higher, while the interleukin-12 (Th1 cytokine) level was significantly lower, in those with anti-HEV IgG positivity. Of five schizophrenia patients who were anti-HEV IgM positive, four had elevated CD4 ? /CD8 ? T-cell ratios. HEV RNA was isolated from one of these four patients and classified as genotype 4. Anti-HEV IgM positivity was not detected among healthy controls. Therefore, schizophrenia patients exhibited a higher risk of HEV infection than controls.
Output: Increased risk of hepatitis E virus infection in schizophrenia
HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a Cterminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis. The overall structures, especially the residues in some positions of HR2 are highly conserved. Fourteen hydrophobic and three polar residues from each HR1 peptide are packed in layers at the coiledcoil interface. These core amino acids can be grouped into seven heptad repeats. Analysis of hydrophobic and hydrophilic interactions between HR2 helix and HR1 helices, shows that the HR1 and HR2 polypeptides are highly complementary in both shape and chemical properties. Furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting membrane fusion, a crucial step of HCoV-229E infection.
Output: Structural characterization of the HCoV-229E fusion core
Stable isotope labeling is central to NMR studies of nucleic acids. Development of methods that incorporate labels at specific atomic positions within each nucleotide promises to expand the size range of RNAs that can be studied by NMR. Using recombinantly expressed enzymes and chemically synthesized ribose and nucleobase, we have developed an inexpensive, rapid chemo-enzymatic method to label ATP and GTP site specifically and in high yields of up to 90%. We incorporated these nucleotides into RNAs with sizes ranging from 27 to 59 nucleotides using in vitro transcription: A-Site (27 nt), the iron responsive elements (29 nt), a fluoride riboswitch from Bacillus anthracis (48 nt), and a frame-shifting element from a human corona virus (59 nt). Finally, we showcase the improvement in spectral quality arising from reduced crowding and narrowed linewidths, and accurate analysis of NMR relaxation dispersion (CPMG) and TROSY-based CEST experiments to measure sms time scale motions, and an improved NOESY strategy for resonance assignment. Applications of this selective labeling technology promises to reduce difficulties associated with chemical shift overlap and rapid signal decay that have made it challenging to study the structure and dynamics of large RNAs beyond the 50 nt median size found in the PDB.
Output: Chemo-enzymatic synthesis of site-specific isotopically labeled nucleotides for use in NMR resonance assignment, dynamics and structural characterizations
Bovine viral diarrhea virus (BVDV) is a pestivirus member of the Flaviviridae family, closely related to, and used as a surrogate model for the hepatitis C virus. Its envelope contains the E1 and E2 glycoproteins, disulfide linked into homo-and heterodimers. In this study, we investigate the role of disulfide bond formation in the folding, assembly, and stability of BVDV glycoproteins. We provide molecular evidence that intact disulfide bonds are critical for the acquirement of a stable conformation of E2 monomers. Forcing the E2 glycoproteins to adopt a reduced conformation either co-or post-translationally before assembly into dimers, determines their misfolding and degradation by proteasome. In contrast, dimerization of E2 glycoproteins results in a conformation resistant to reducing agents and degradation. Furthermore, inhibition of the ER-a-mannosidase activity leads to impairment of misfolded E2 degradation, demonstrating the involvement of this enzyme in targeting viral proteins towards proteasomal degradation. Ó
Output: Role of disulfide bond formation in the folding and assembly of the envelope glycoproteins of a pestivirus
Coronaviruses (CoVs) infect humans and many animal species, and are associated with respiratory, enteric, hepatic, and central nervous system diseases. The large size of the CoV genome and the instability of some CoV replicase gene sequences during its propagation in bacteria, represent serious obstacles for the development of reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these limitations, several alternatives to more conventional plasmid-based approaches have been established in the last 13 years. In this report, we briefly review and discuss the different reverse genetic systems developed for CoVs, paying special attention to the severe acute respiratory syndrome CoV (SARS-CoV).
Output: Reprint of: Coronavirus reverse genetic systems: Infectious clones and replicons ଝ
At the height of the SARS 1 crisis in spring 2003, the World Health Organization (WHO) and China fought a silent battle over the prevalence of two competing norms in global health governance. On the one hand, the established norm of sovereignty, particularly the principle of non-interference, had structured a regime for dealing with infectious disease outbreaks that provided ground rules of conduct but ascribed decision-making authority to member states alone. It explicitly ruled out foreign or supranational interference. On the other hand, the emerging norm of global health security was built on an understanding of infectious disease outbreaks as international security problems requiring supranational coordination and governance capacity. In effect, it implied the subordination of national economic and political interests to global disease detection and containment efforts. Its proponents thus sought a prominent role for the WHO in taking decisions in response to global health emergencies which would entail interference with state sovereignty. By the time of the SARS outbreak, this normative tension was far from being resolved. On the contrary, the two central actors in this episode, the Chinese government and the WHO secretariat, turned it into a manifest norm conflict by demonstrating incompatible positional differences over the relative priority of the two norms. 2 Intriguingly, however, neither China nor the WHO resorted to discursive modes of contestation by justifying their respective positions with reference to normative arguments. Almost exclusively, they displayed incompatible normative expectations in the way they put the norms into practice. The WHO acted as if the norm of global health security had already been widely accepted, supplanting those aspects of the sovereignty norm with which it conflicted. Without prior legal or political authorization to do so, the organization took a set of unprecedented measures. Most importantly, it issued travel warnings for affected regions, devised emergency recommendations, and put pressure on governments (the Chinese in particular) to comply-clearly challenging the non-interference 1 Severe Acute Respiratory Syndrome. 2 On the manifestation of norm conflicts, see Michael Zürn, Benjamin Faude and Christian Kreuder-Sonnen, Overlapping spheres of authority and interface conflicts in the global order: introducing a DFG research group, WZB
Output: China vs the WHO: a behavioural norm conflict in the SARS crisis
Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in progressively infected cats. While testing/removal and vaccination led to a decreased prevalence of FeLV, recently, this decrease has reportedly stagnated in some countries. This study aimed to prospectively determine the prevalence of FeLV viraemia in cats taken to veterinary facilities in 32 European countries. FeLV viral RNA was semiquantitatively detected in saliva, using RT-qPCR as a measure of viraemia. Risk and protective factors were assessed using an online questionnaire to report geographic, demographic, husbandry, FeLV vaccination, and clinical data. The overall prevalence of FeLV viraemia in cats visiting a veterinary facility, of which 10.4% were shelter and rescue cats, was 2.3% (141/6005; 95% CI: 2.0%-2.8%) with the highest prevalences in Portugal, Hungary, and Italy/Malta (5.7%-8.8%). Using multivariate analysis, seven risk factors (Southern Europe, male intact, 1-6 years of age, indoor and outdoor or outdoor-only living, living in a group of ≥5 cats, illness), and three protective factors (Northern Europe, Western Europe, pedigree cats) were identified. Using classification and regression tree (CART) analysis, the origin of cats in Europe, pedigree, and access to outdoors were important predictors of FeLV status. FeLV-infected sick cats shed more viral RNA than FeLV-infected healthy cats, and they suffered more frequently from anaemia, anorexia, and gingivitis/stomatitis than uninfected sick cats. Most cats had never been FeLV-vaccinated; vaccination rates were indirectly associated with the gross domestic product (GDP) per capita. In conclusion, we identified countries where FeLV was undetectable, demonstrating that the infection can be eradicated and highlighting those regions where awareness and prevention should be increased. supervision, methodology, R.H.-L., M.L.M., and H.L.; project administration and resources, H.L. and R.H.-L.; funding acquisition, H.L.; project administration (communication with country representatives and local veterinarians), investigation, N.S. and E.G.; project administration (country representatives: local administration including translation, interaction with the local veterinarians, sample collection and returning):
Output: Pan-European Study on the Prevalence of the Feline Leukaemia Virus Infection -Reported by the European Advisory Board on Cat Diseases (ABCD Europe)
Biological integrity Wholeness of a living system, including the capacity to sustain the full range of organisms and processes having evolved in a region. Biosphere The thin layer of life at or near the surface of the Earth. Biota Living things, in particular, the flora and fauna of a region. Biotic impoverishment Systematic reduction in Earth's capacity to support life. Ecosystem engineers Organisms that physically shape their environment, including organisms that create or modify the environments of other organisms. Environment Surroundings; the complex of physical, chemical, and biotic factors acting upon a living system and influencing its form, function, and survival. Health A flourishing condition, well-being; capacity for self-renewal. Impact A forceful contact; a major effect of one thing on another.
Output: Environmental Impact, Concept and Measurement of
Cell fusion is a ubiquitous process fundamental to physiological and pathophysiological events common to multiple cell types and species. Performed ex vivo , cell fusion is a versatile research and therapeutic tool for gene mapping, antibody production, discovering new mechanisms in biological processes, inventing alternative therapies for cell reprogramming, restoring organ function, and creating cellular therapeutics for cancer treatment. Cell fusion can be successfully applied by creating cellular therapeutic of donor -recipient chimeric cell (DRCC) in the fi eld of solid organ and vascularized composite allotransplantation (VCA). Immunomodulatory DRCC therapy has the potential to reduce or even eliminate the need for toxic, life-long immunosuppression and to prevent both acute and chronic rejection. This innovative VCA treatment is a combination of ex vivo created chimeric cell therapy with a short-term selective protocol of monoclonal antibody and Cyclosporine A. The utilization of short-term immunosuppressive protocol will provide the opportunity for chimeric cell engraftment, proliferation, and re-education of recipient's immune system resulting in prolongation of allograft survival. The use of chimeric cells, as a supportive treatment for VCA, would improve the conditions of severely disfi gured patients by offering safe alternative approach and providing better functional and aesthetic results compared to standard reconstructive procedures.
Output: 72 Cellular Therapy Models: Ex Vivo Chimera Model by Cell Fusion
Background: Microbiology reference laboratories are critical in the development of high-quality clinical and public health services. In Belgium, the reference laboratories performed their activities on a voluntary basis and lacked a legal status. Methods: Pathogens or groups of pathogens necessitating a national reference center (NRC) were prioritized based on diagnostic and epidemiologic relevance. Terms of reference for each of these pathogens were developed. Results: Recently, 40 NRCs for different pathogens or groups of pathogens have been installed in Belgium to fulfill the following core functions: offering reference diagnostics, collecting reference materials, sharing information and scientific advice, participating in national and international networks, collaborating with research workgroups, and contributing to surveillance activities. Conclusions: These NRCs are important focal points of the national and international network in public health microbiology.
Output: Establishment and reinforcement of the national reference centers for human microbiology in Belgium
Background and Objective: Viruses are infectious agents that replicate inside organisms and reveal a plethora of distinct characteristics. Viral infections spread in many ways, but often have devastating consequences and represent a huge danger for public health. It is important to design statistical and computational techniques capable of handling the available data and highlighting the most important features. Methods: This paper reviews the quantitative and qualitative behaviour of 22 infectious diseases caused by viruses. The information is compared and visualized by means of the multidimensional scaling technique. The results are robust to uncertainties in the data and revealed to be consistent with clinical practice. The paper shows that the proposed methodology may represent a solid mathematical tool to tackle a larger number of virus and additional information about these infectious agents. c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 1 3 1 ( 2 0 1 6 ) 9 7 -1 1 0 j o u r n a l h o m e p a g e : w w w. i n t l . e l s e v i e r h e a l t h . c o m / j o u r n a l s / c m p b
Output: Multidimensional scaling analysis of virus diseases
Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptorbinding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.
Output: Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
Background: Emergency departments (EDs) are the basic units of emergency care. We performed a national inventory of all Singapore EDs and describe their characteristics and capabilities. Methods: Singapore EDs accessible to the general public 24/7 were surveyed using the National ED Inventories instrument (www.emnet-nedi.org). ED staff members were asked about ED characteristics with reference to calendar year 2007. Results: Fourteen EDs participated (100% response). All EDs were located in hospitals, and most (92%) were independent departments. One was a psychiatric ED; the rest were general EDs. Among general EDs, all had a contiguous layout, with medical and surgical care provided in one area. All but two EDs saw both adults and children; one ED was adult-only, and the other saw only children. Six were in the public sector and seven in private health-care institutions, with public EDs seeing the majority (78%) of ED patients. Each private ED had an annual patient census of <30,000. These EDs received 2% of ambulances and had an inpatient admission rate of 7%. Each public ED had an annual census of >60,000. They received 98% of ambulances and had an inpatient admission rate of 30%. Two public EDs reported being overcapacity; no private EDs did. For both public and private EDs, availability of consultant resources in EDs was high, while technological resources varied. Conclusion: Characteristics and capabilities of Singapore EDs varied and were largely dependent on whether they are in public or private hospitals. This initial inventory establishes a benchmark to further monitor the development of emergency care in Singapore.
Output: National inventory of emergency departments in Singapore
When the central nervous system (CNS) is under viral attack, defensive antiviral responses must necessarily arise from the CNS itself to rapidly and efficiently curb infections with minimal collateral damage to the sensitive, specialized and non-regenerating neural tissue. This presents a unique challenge because an intact blood-brain barrier (BBB) and lack of proper lymphatic drainage keeps the CNS virtually outside the radar of circulating immune cells that are at constant vigilance for antigens in peripheral tissues. Limited antigen presentation skills of CNS cells in comparison to peripheral tissues is because of a total lack of dendritic cells and feeble expression of major histocompatibility complex (MHC) proteins in neurons and glia. However, research over the past two decades has identified immune effector mechanisms intrinsic to the CNS for immediate tackling, attenuating and clearing of viral infections, with assistance pouring in from peripheral circulation in the form of neutralizing antibodies and cytotoxic T cells at a later stage. Specialized CNS cells, microglia and astrocytes, were regarded as sole sentinels of the brain for containing a viral onslaught but neurons held little recognition as a potential candidate for protecting itself from the proliferation and pathogenesis of neurotropic viruses. Accumulating evidence however indicates that extracellular insult causes neurons to express immune factors characteristic of lymphoid tissues. This article aims to comprehensively analyze current research on this conditional alteration in the protein expression repertoire of neurons and the role it plays in CNS innate immune response to counter viral infections. ß
Output: Neurons under viral attack: Victims or warriors?