niryuu/sni-each-converted huggingface dataset:
Objective: The aim of this study was to analyze the etiology and clinical consequences of viral respiratory infections in 18 elderly care centers (ECC) in Lisbon, which housed a total of 1022 residents. Methods: Nasopharyngeal swabs were collected whenever an elderly had symptoms of acute respiratory infections (ARI). PCR and RT-PCR were performed for influenza A/B, human parainfluenza virus 1-4, adenovirus, human metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus, enterovirus, human coronavirus and human Bocavirus (HBoV). Array cards for atypical bacteria were also used in severe cases. Results: In total, 188 episodes of ARI were reported, being rhinovirus the most frequently detected (n = 53), followed by influenza A(H3) (n = 19) and HBoV (n = 14). Severe infections were reported in 19 patients, 11 of which were fatal, Legionela pneumophila, rhinovirus, HMPV and RSV associated with these fatalities. Nine influenza strains were analyzed, all antigenically dissimilar from vaccine strain 2013/14. "Age", "HMPV" and "Respiratory disease" showed an association with severe infection. Conclusions: In this study an etiologic agent could be found in 60% of the acute respiratory episodes. These data provides information about the circulating viruses in ECC and highlights the importance of searching both viruses and atypical bacteria in severe ARI.
Output: Respiratory infections in elderly people: Viral role in a resident population of elderly care centers in Lisbon
Background: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. Methods: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. Results: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. Conclusions: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.
Output: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics
Monoclonal antibodies (MAbs) directed against herpes simplex virus (HSV)-coded glycoproteins gB, gC, gD and gE were employed in an in vitro model of neuroinvasiveness using sensory neurons from rat dorsal root ganglion (DRG) cells . The neurons were cultured in a two-chamber system allowing infection via the neuritic extensions exclusively . The effects of 30 MAbs on viral replication of the encephalitis-derived HSV-1 strain 2762 and its less neuroinvasive variant 2762p11 were assayed in this model . One MAb reactive with gD gave a nine-fold reduction of the virus yields of both strains . One MAb directed against gB gave an enhanced virus yield of strain 2762, but not of the 2762p11 variant . Another gB-reactive MAb decreased the virus yield of strain 2762pll, but not of 2762 after neuritic infection . The findings indicate that an alteration of gB has occurred during the passage of the strain 2762 . Mutants of the same strain were derived by infecting hybridomas producing MAb reactive with gB, gC, gD and gE, respectively . The gB hybridoma mutant showed a significantly lower neuroinvasiveness in the DRG model, and was non-virulent after snout infection of mice . We suggest that the structure of gB of the strain 2762 is of importance for the neuroinvasiveness of this strain .
Output: Mapping neuroinvasiveness of the herpes simplex virus type 1 encephalitis-inducing strain 2762 by the use of monoclonal antibodies
Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005-07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts.
Output: Chikungunya: A Potentially Emerging Epidemic?
Introduction: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. Methods: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. Results: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. Conclusions: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.
Output: Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice
Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system. Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of 2 of 55 high-dimensional and complex experimental data. Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science. The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches. The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets. A major benefit of such an environment is the possibility of connecting different tools into more complex workflows. Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research. This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis. Multifunctional workflows, possible user interfaces and integration into workflow management systems are also reviewed. In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub.
Output: metabolites H OH OH The metaRbolomics Toolbox in Bioconductor and beyond
Air distributions in commercial airliner cabins are crucial for creating a thermally comfortable and healthy cabin environment. This paper reviews the methods used in predicting, designing, and analyzing air distributions in the cabins, among which experimental measurements and numerical simulations are the two popular ones. The experimental measurements have usually been seen as more reliable although they are more expensive and time consuming. Most of the numerical simulations use Computational Fluid Dynamics (CFD) that can provide effectively detailed information. Numerous applications using the two methods can be found in the literature for studying air distributions in aircraft cabins, including investigations on more reliable and accurate models. The review in the paper shows that the studies using both experimental measurements and computer simulations are becoming popular. And it is necessary to use a full-scale test rig to obtain reliable and high quality experimental data. What's more, the hybrid CFD models are found to be rather promising for simulating air distributions in airliner cabins.
Output: State-of-the-art methods for studying air distributions in commercial airliner cabins
Microwave has been extensively applied to inactivate microorganisms in liquids, food, and surfaces. However, energy efficiency is a limiting factor for the environmental application. The utilization pathway and energy efficiency of the microwave in different media have not been investigated. In this study, the inactivation performance, energy utilization, and bactericidal mechanisms for microwave-irradiated airborne and waterborne Escherichia coli were compared. A Beer-Lambert law-based model was also developed and validated to compare the inactivation performance in different phases. Microwave had greater inactivation effect on airborne bacteria than waterborne bacteria. The inactivation rate constant for airborne E. coli (0.29 s −1 ) was nearly 20 times higher than that of waterborne species (0.014 s −1 ). Most of the absorbed microwave energy (92.3%) was converted to increase water temperature instead of inactivating the waterborne bacteria, because the microwave photons were easily absorbed by water molecules. By contrast, 45.4% of the absorbed energy could disinfect the airborne bacteria. Finally, the required energies for 1-log inactivation were calculated as 2.3 J and 116.9 J per log-inactivation for airborne and waterborne E. coli, respectively. The airborne and waterborne E. coli samples showed distinct microwave inactivation mechanisms. Waterborne E. coli disinfection was primarily due to thermal effect, while the non-thermal effect was the major mechanism for airborne E. coli inactivation.
Output: Airborne disinfection using microwave-based technology: Energy efficient and distinct inactivation mechanism compared with waterborne disinfection
A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the b-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to recolonization with a different isolate, observed exclusively among b-lactams treated patients. Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).
Output: Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study
Graphical Abstract Highlights d IFN-gamma inhibits murine norovirus replication complexes via the LC3 conjugation system d Degradative autophagy is not required to affect LC3mediated RC restriction d LC3 and IFN-inducible GTPases are targeted to the RC membrane d IFN-inducible GTPases are required to inhibit MNV replication in mice and humans SUMMARY All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associatedprotein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.
Output: Viral Replication Complexes Are Targeted by LC3- Guided Interferon-Inducible GTPases Article Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases
We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/ΔF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/ΔF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/ΔF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pigadapted EBOV.
Output: Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. v a c u n a s . 2 0 1 9;2 0(2):53-59 a b s t r a c t Introduction: Influenza is a common respiratory infectious disease affecting population worldwide yearly. The aim of this work is to describe the 2017-2018 influenza season and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group. Methods: Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital. Analysis of data by Chi-squared, ANOVA, multiple regression and negative control test or case to case for vaccine effectiveness assessment in primary care and SHLCI respectively. Results: Moderate-high intensity and early onset season with predominance of influenza B virus (IVB) (63%) followed by an increase of circulation of influenza A virus (IVA). A total of 419 IV from primary care samples. Vaccine effectiveness (VE) in primary care setting was 14% (95%CI: 0-47%). 1306 severe cases (adjusted cumulative incidence 18.54/100,000 inhabitants (95%CI: 17.54-19.55)). The highest proportion of severe cases were in the >64 (65.1%) (aOR 15.70; 95%CI: 12.06-20.46; p < 0.001) followed by 45-64 yo (25.4%) (aOR 6.03; 95%CI: 4.57-7.97). VE in preventing intensive care unit (ICU) admission was 35% (95%CI: 10-54%). Final outcome death while hospitalized occurred in 175 SHLCI cases with a case fatality rate of 13.4%. Conclusions: 2017-2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group. Conclusiones: La temporada de gripe 2017-2018 fue una temporada epidémica inusual con un inicio temprano, gran predominio del VGB (cepa Yamagata) con una elevada tasa de hospitalización de casos graves en ancianos, lo que subraya la necesidad de mejorar la aceptación de la vacuna en este grupo de edad.
Output: Vacunas Original Seasonal influenza surveillance: Observational study on the 2017-2018 season with predominant B influenza virus circulation
Neonatal necrotizing enterocolitis which develops after feeding preterm infants is characterized by severe intestinal inflammation and profound systemic metabolic acidosis. The fermentation of undigested dietary carbohydrate by colonic flora yields gases (CO 2 and H 2 ) and short chain organic acids. These organic acids can disrupt the intestinal mucosa and initiate inflammation driven predominantly by resident mast cells and by granulocytes which are recruited from blood. A systemic acidosis ensues derived from intestinal acids, not classic lactic acidosis produced from anaerobic metabolism. The systemic acidosis further compromises inflamed bowel leading to bowel necrosis.
Output: Feeding associated neonatal necrotizing enterocolitis (Primary NEC) is an inflammatory bowel disease
Like most viruses that replicate in the cytoplasm, mammalian reoviruses assemble membranous neo-organelles called inclusions that serve as sites of viral genome replication and particle morphogenesis. Viral inclusion formation is essential for viral infection, but how these organelles form is not well understood. We investigated the biogenesis of reovirus inclusions. Correlative light and electron microscopy showed that endoplasmic reticulum (ER) membranes are in contact with nascent inclusions, which form by collections of membranous tubules and vesicles as revealed by electron tomography. ER markers and newly synthesized viral RNA are detected in inclusion internal membranes. Live-cell imaging showed that early in infection, the ER is transformed into thin cisternae that fragment into small tubules and vesicles. We discovered that ER tubulation and vesiculation are mediated by the reovirus NS and NS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles. IMPORTANCE Viruses modify cellular structures to build replication organelles. These organelles serve as sites of viral genome replication and particle morphogenesis and are essential for viral infection. However, how these organelles are constructed is not well understood. We found that the replication organelles of mammalian reoviruses are formed by collections of membranous tubules and vesicles derived from extensive remodeling of the peripheral endoplasmic reticulum (ER). We also observed that ER tubulation and vesiculation are triggered by the reovirus NS and NS proteins, respectively. Our results enhance an understanding of how viruses remodel cellular compartments to build functional replication organelles and provide functions for two enigmatic reovirus replication proteins. Most importantly, this research uncovers a new mechanism by which viruses form factories for particle assembly.
Output: Reovirus NS and NS Proteins Remodel the Endoplasmic Reticulum to Build Replication Neo-Organelles
Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1-deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT-PCR and western blot, respectively. Human airway epithelial cells that were DNAI1-deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.
Output: Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy
Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.
Output: Addressing the selectivity and toxicity of antiviral nucleosides
In recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. The Chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (SARS), influenza A (H1N1), avian influenza H5N1 and H7N9, and Ebola hemorrhagic fever, while actively maintained public health, economic development, and national construction. This paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases-the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism-and presents a sorted summary of the practices and experiences of cooperative emergency responses to infectious diseases. In the future, the Chinese military and the civilian sector will further strengthen the cooperative joint command system and emergency rescue force and will reinforce their collaborative information-sharing platform and technical equipment system to further improve military-civilian collaborative emergency infectious diseases disposal, advance the level of infectious disease prevention and control, and maintain public health.
Output: Military-civilian cooperative emergency response to infectious disease prevention and control in China
Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
Output: Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
Houttuynia cordata Thunb. is a medicinal plant widely used in folk medicine in several Asian countries. It has been reported that a water extract of H. cordata exhibits activity against herpes simplex virus (HSV) and the virus of severe acute respiratory syndrome (SARS), although the mechanisms are not fully understood yet. Previous studies have demonstrated absolute requirement of NF-jB activation for efficient replication of HSV-1 and HSV-2 and inhibition of NF-jB activation has been shown to suppress HSV infection. Here we show that a hot water extract of H. cordata (HCWE) inhibits HSV-2 infection through inhibition of NF-jB activation. The IC 50 was estimated at 50 lg/ml of lyophilized HCWE powder. At 150 and 450 lg/ml, HCWE blocked infectious HSV-2 production by more than 3 and 4 logs, respectively. The inhibitory activity was concomitant with an inhibition of NF-jB activation by HSV-2 infection. Although activation of NF-jB and Erk MAPK has been implicated for HSV replication and growth, HCWE showed no effect on HSV-2-induced Erk activation. Furthermore, we show that treatment with quercetin, quercitrin or isoquercitrin, major water extractable flavonoids from H. cordata, significantly blocked HSV-2 infection. These results together demonstrated that H. cordata blocks HSV-2 infection through inhibition of NF-jB activation.
Output: Houttuynia cordata blocks HSV infection through inhibition of NF-jB activation
This chapter mentions some other groundbreaking innovations and technological improvements that came along after the crisis. The recent attempts at creating digital currencies, famously known as cryptocurrencies, and their corresponding platform blockchain were some of these. How and why did they emerge? What do their inventions imply for our future? And why are they important? Sharing economy and memberships (as opposed to ownerships) are other examples of profound changes. Increasing use of shared goods, services like Uber and Airbnb, and the unstoppable trend of membership services like e-newspapers, e-libraries, and music streaming points to one conclusion: the end of the idea of ownership. On the governmental side, we have been observing an increasing inclination toward authoritarian states. Liberalism seems to have failed. People have been losing their trust in economic regimes. My argument in this chapter is that without the 2008 crisis, there would have never been these developments and innovations.
Output: The Crisis and Aftermath-II: Society and Economics
Background: Rift Valley fever (RVF) is endemic to the tropical regions of eastern and southern Africa. The seroprevalence of RVF was investigated among the human population in Borno State, Nigeria to determine the occurrence of the disease in the study area in comparison with that of Lassa fever and Crimean-Congo Hemorrhagic fever. Methods: Recombinant nucleoprotein (rNP)-based IgG-ELISAs for the detection of serum antibodies against RVF virus (RVFV), Lassa fever virus (LASV), and Crimean-Congo hemorrhagic fever virus (CCHFV) were used to test human sera in Borno State, Nigeria. The presence of neutralizing antibody against the RVFV-glycoprotein-bearing vesicular stomatitis virus pseudotype (RVFVpv) was also determined in the human sera. Of the 297 serum samples tested, 42 (14.1%) were positive for the presence of RVFV-IgG and 22 (7.4%) and 7 (2.4%) of the serum samples were positive for antibodies against LASV and CCHFV, respectively. There was a positive correlation between the titers of neutralizing antibodies obtained using RVFVpv and those obtained using the conventional neutralization assay with the attenuated RVFV-MP12 strain. Conclusions: The seroprevalence of RVF was significantly higher than that of LASV and CCHF in Borno State, Nigeria. The RVFVpv-based neutralization assay developed in this study has the potential to replace the traditional assays based on live viruses for the diagnosis and seroepidemiological studies of RVF.
Output: Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria
Socio-economic factors are widely believed to have been an important driver of the transmission of Ebola Virus Disease (EVD) during the West African outbreak of 2014-16, however, studies that have investigated the relationship between socio-economic status (SES) and EVD have found inconsistent results. Using nationally representative household survey data on whether respondents knew a close friend or family member with Ebola, we explore the SES determinants of EVD exposure along individual, household, and community lines in Liberia and Sierra Leone. While we find no overall association between household wealth and EVD exposure, we find that pooled data mask important differences observed within countries with higher wealth households more likely to have been exposed to EVD in Sierra Leone and the opposite relationship in Liberia. Finally, we also generally find a positive association between education and EVD exposure both at the individual and the community levels in the full sample. There is an urgent need to better understand these relationships to examine both why the outbreak spread and to help prepare for future outbreaks.
Output: -NC-ND license The socio-economic distribution of exposure to Ebola: Survey evidence from Liberia and Sierra Leone
Recent cases of emergent diseases have renewed interest in the evolutionary and ecological mechanisms that promote parasite adaptation to novel hosts [1] [2] [3] [4] [5] [6] . Crucial to adaptation is the degree of mixing of original, susceptible hosts, and novel hosts. An increase in the frequency of the original host has two opposing effects on adaptation: an increase in the supply of mutant pathogens with improved performance on the novel host [7-9]; and reduced selection to infect novel hosts, caused by fitness costs commonly observed to be associated with host switching [10] [11] [12] [13] [14] [15] [16] [17] . The probability of disease emergence will therefore peak at intermediate frequencies of the original host. We tested these predictions by following the evolution of a virus grown under a range of different frequencies of susceptible (original) and resistant (novel) host bacteria. Viruses that evolved to infect resistant hosts were only detected when susceptible hosts were at frequencies between 0.1% and 1%. Subsequent experiments supported the predictions that there was reduced selection and mutation supply at higher and lower frequencies, respectively. These results suggest that adaptation to novel hosts can occur only under very specific ecological conditions, and that small changes in contact rates between host species might help to mitigate disease emergence.
Output: Report Host Mixing and Disease Emergence
To study the influence of a linker rigidity and donor-acceptor properties, the P-CH 2 -O-CHR-fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the P-CH 2 -HN-C(O)-residue. The respective phosphonates were synthesized in good yields by coupling the straight chain of x-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on the 1 H and 13 C NMR data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates from series a and b was confirmed. For phosphonates containing 1,3-propylidene (series c) fragments, antiperiplanar disposition of the bulky O,O-diethylphosphonate and substituted amidomethyl groups was established. The synthesized ANPs P-X-HNC(O)-CH 2 B (X = CH 2 , CH 2 CH 2 , CH 2-CH 2 CH 2 , CH 2 OCH 2 CH 2 ) appeared inactive in antiviral assays against a wide variety of DNA and RNA viruses at concentrations up to 100 lM while marginal antiproliferative activity (L1210 cells, IC 50 = 89 ± 16 lM and HeLa cells, IC 50 = 194 ± 19 lM) was noticed for the analog derived from (5-fluorouracyl-1-yl)acetic acid and O,O-diethyl (2-aminoethoxy)methylphosphonate. O H N X (EtO) 2 (O)P X = CH 2 , CH 2 CH 2 , CH 2 CH 2 CH 2 , CH 2 OCH 2 CH 2 B = natural or modified nuclebases
Output: Acyclic nucleoside phosphonates containing the amide bond
Porcine aminopeptidase N (pAPN) is a common cellular receptor for swine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV). To investigate single-chain fragment variable (scFv) repertoire against pAPN, the genes encoding the immunoglobulin light chain variable region (VL) and heavy chain variable region (VH) were amplified by reverse transcript polymerase chain reaction (RT-PCR) using a series of degenerate primers from the spleen of BABL/c mice immunized with native pAPN. The VL and VH amplicons were combined randomly by a 12 amino acid flexible linker by splicing by overlap extension PCR (SOE-PCR), which produced the scFv gene repertoire. After ligation of the scFv gene repertoire into the T7Select10-3b vector, a mouse scFv phage library specific for pAPN was produced through in vitro packaging. The primary scFv library against pAPN contained 2.0 × 10 7 recombinant phage clones, and the titer of the amplified library was 3.6 × 10 9 pfu/mL. BstNI restriction analysis and DNA sequencing revealed that 28 phage clones from the primary pAPN scFv library showed excellent diversity. The effectiveness of the scFv library against pAPN was verified further by phage ELISA using the recombinant protein of the pAPN C subunit as coating antigen. The construction and evaluation of a murine scFv library against the common receptor pAPN of porcine coronaviruses TGEV and PEDV using the T7 phage display system are described.
Output: Generation of a mouse scFv library specific for porcine aminopeptidase N using the T7 phage display system
An antigenic variant of avian infectious bronchitis virus (IBV), a coronavirus, was isolated and characterized. This strain, CUT2, possesses a number of unusual features, which have not been previously observed in IBV. The S1 glycoprotein of CU-T2 carries virus-neutralizing and serotype-specific epitopes of two IBV serotypes, Arkansas (Ark) and Massachusetts (Mass). Sequence analysis revealed that the virus, originally an Ark serotype, has acquired the Mass-specific epitope by mutation(s). This provides evidence that point mutations may lead to generation of IBV antigenic variants in the field. It was further observed that two independent recombination events involving three different IBV strains had occurred in the $2 glycoprotein gene and N protein gene of CU-T2, indicating that genomic RNA recombination in IBV may occur in multiple genes in nature. It was especially significant that a sequence of Holland 52 (a vaccine strain) had replaced half of the N gene of CU-T2. This proves that recombination among vaccine strains is contributing to the generation of IBV variants in the field. Based on these observations it is predicted that every IBV field isolate could have unique genetic nature. Therefore, several recently reported diagnostic and serotyping methods of IBV which are based on dot-blot hybridization, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR), may not reveal the true antigenic and/or genetic nature of IBV isolates, and may in fact yield misleading information.
Output: A novel variant of avian infectious bronchitis virus resulting from recombination among three different strains
The SARS-CoV spike protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two peptides denoted HR-N(SN50) and HR-C(SC40), corresponding to the Leu/Ile/Val-rich heptad-repeat regions from the N-terminal and C-terminal segments of the SARS-CoV spike S2 sequence, respectively, were synthesized and predicted to form trimeric assembly of hairpin-like structures. The polyclonal antibodies produced by recombinant S2 protein were tested for antigenicity of the two heptad repeats. We report here the first crystallographic study of the SARS spike HR-N/HR-C complex. The crystal belongs to the triclinic space group P1 and the data-set collected to 2.98 Å resolution showed noncrystallographic pseudo-222 and 3-fold symmetries. Based on these data, comparative modeling of the SARS-CoV fusion core was performed. The immunological and structural information presented herein may provide a more detailed understanding of the viral fusion mechanism as well as the development of effective therapy against SARS-CoV infection.
Output: Immunological, structural, and preliminary X-ray diffraction characterizations of the fusion core of the SARS-coronavirus spike protein q
The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap 4 A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap 4 A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap 4 A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap 4 A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap 4 A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap 4 A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.
Output: SARS coronavirus protein 7a interacts with human Ap 4 A-hydrolase
The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.
Output: Viral factors in influenza pandemic risk assessment
Tuberculosis (TB) is a disease which is caused by a relatively large, non-motile, rod-shaped pathogen called Mycobacterium tuberculosis. TB is a major cause of illness and death worldwide, especially in Asia and Africa. Despite the fact that TB is a curable illness, the tragedy is that TB remains the biggest killer in the world as a single pathogen. The aim of this study was to determine the experiences of nurses caring for TB patients at a regional hospital in Limpopo Province, South Africa. Qualitative, exploratory, and descriptive designs were used. A non-probability purposive sampling method was used to select the participants. The personal experiences of six nurses with more than five years' experience caring for TB patients at a regional hospital were explored, and it was guided by data saturation. Data were collected through in-depth individual interviews. Data were analyzed using Colaizzi's method. Trustworthiness was ensured and ethical considerations were observed in this study. The research findings revealed six major themes from the raw data: challenges of the working environment, problems impacting on the quality of nursing care, fear, anxiety, stress and risk of contracting infection, nurses' perceptions towards patients, support structure available in the hospital, and support needs for the nurses. Therefore, there is an urgent need to address the challenges experienced by nurses caring for communicable diseases through provision of a positive practice work environment.
Output: Caring for Tuberculosis Patients: Understanding the Plight of Nurses at a Regional Hospital in Limpopo Province, South Africa
Malectin is a carbohydrate-binding lectin protein found in the endoplasmic reticulum (ER). It selectivity binds to Glc 2 -N-glycan and is involved in a glycoprotein quality control mechanism. Even though malectin may play a role in immunity, its role in innate immunity is not fully known. In the present study, we identified and characterized the malectin gene from Hippocampus abdominalis (HaMLEC). We analyzed sequence features, spatial expression levels, temporal expression profiles upon immune responses, bacterial and carbohydrate binding abilities and anti-viral properties to investigate the potential role of HaMLEC in innate immunity. The molecular weight and isoelectric point (pI) were estimated to be 31.99 kDa and 5.17, respectively. The N-terminal signal peptide, malectin superfamily domain and C-terminal transmembrane region were identified from the amino acid sequence of HaMLEC. The close evolutionary relationship of HaMLEC with other teleosts was identified by phylogenetic analysis. According to quantitative PCR (qPCR) results, HaMLEC expression was observed in all the examined tissues and high expression was observed in the ovary and brain, compared to other tested tissues. Temporal expression of HaMLEC in liver and blood tissues were significant modulated upon exposure to immunogens Edwardasiella tarda, Streptococcus iniae, polyinosinic:polycytidylic and lipopolysaccharide. The presence of carbohydrate binding modules (CBMs) of bacterial glycosyl hydrolases were functionally confirmed by a bacterial binding assay. Anti-viral activity significantly reduced viral hemorrhagic septicemia virus (VHSV) replication in cells overexpressing HaMLEC. The observed results suggested that HaMLEC may have a significant role in innate immunity in Hippocampus abdominalis.
Output: Molecular and functional insights into a novel teleost malectin from big- belly seahorse Hippocampus abdominalis
First identified in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death, with a case fatality rate of~35%. An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. The murine dipeptidyl peptidase 4 (Dpp4) protein is not a functional receptor for MERS-CoV; thus, mice are resistant to MERS-CoV infection. We generated human DPP4 knock-in (hDPP4 KI) mice by replacing exons 10-12 at the mouse Dpp4 locus with exons 10-12 from the human DPP4 gene. The resultant human DPP4 KI mice are permissive to MERS-CoV (HCoV-EMC/2012 strain) infection but develop no disease. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. After 30 in vivo passages, an adapted virus clone was isolated and designated MERS MA 6.1.2. This virus clone produced significantly higher titers than the parental clone in the lungs of hDPP4 KI mice and caused diffuse lung injury and a fatal respiratory infection. In this chapter, we will describe in detail the procedures used to mouse adapt MERS-CoV by serial passage of the virus in lungs. We also describe the methods used to isolate virus clones and characterize virus infection.
Output: Chapter 13 Development of a Mouse-Adapted MERS Coronavirus