niryuu/sni-each-converted huggingface dataset:
Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an antiviral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs.
Output: Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus
autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.
Output: SARS Coronavirus Fusion Peptide- Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice OPEN
For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. Ultimately, these kinases, and the cellular signaling pathways that they exploit, may serve as therapeutic targets for treating patients. Currently, small molecule inhibitors of kinases are under investigation as therapy for herpes viral infections. Additionally, a number of cellular or host-directed tyrosine kinase inhibitors that have been previously FDA-approved for cancer treatment are under study in animal models and clinical trials, as they have shown promise for the treatment of various viral infections as well. This review will highlight the wide range of viral proteins phosphorylated by viral and cellular kinases, and the potential for variability of kinase recognition sites within viral substrates to impact phosphorylation and kinase prediction. Research studying kinase-targeting prophylactic and therapeutic treatments for a number of viral infections will also be discussed.
Output: Phosphorylation events during viral infections provide potential therapeutic targets
Throughout the book chapters, researchers have highlighted the recent advancement in microfluidic areas, particularly those involving microdroplets. Simon and Lee focused on microfluidics droplet manipulations and applications, including droplet fusion, droplet fission, mixing in droplets, and droplet sorting. By combining these operations, they have shown promising applications in executing chemical reactions and biological assays at the microscale. Day and Karimiani discussed dropletisation of bio-reactions. Zhang and Liu elaborated the physics involved in multiphase flows and microdroplets dynamics. They emphasized the important dimensionless parameters relating to droplet dynamics with droplet generation process as an example. Barber and Emerson discussed the fundamental droplet handling operations and the recent advances in electrowetting microdroplet technologies. They also provided an overview of droplet-based electrowetting technologies in biological and chemical applications. P. Neuzil
Output: Trends and Perspectives
Choice of interaction function is one of the most important parts for modelling a food chain. Many models have been proposed as a diseased-prey predator model with Holling type-I or type-II or type-III interactions, but there is no model with general Holling type interactions. In this paper, we study a diseased prey-predator model with general Holling type interactions. Local stability conditions of equilibrium points are derived. We obtain the permanence and impermanence conditions of the system. The conditions for global stability of the system are also derived. The system exhibits limit cycle, period-2, higher periodic oscillations and chaotic behaviour for different values of Holling parameters. One parameter bifurcation analysis is done with respect to general Holling parameters and infection rate. We utilize the MATCONT package to analyse the detailed bifurcation scenario as the two important interaction parameters are varied. It is interesting to note that a diseased system becomes a disease free system for proper choice of interaction functions. Our results give an idea for constructing a realistic food chain model through proper choice of general Holling parameters.
Output: Diseased prey predator model with general Holling type interactions
Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects. (J Allergy Clin Immunol 2005;116:1334-42.) 
Output: Basic and clinical immunology Current perspectives Innate immunity for biodefense: A strategy whose time has come
Background: Porcine circovirus type 2 (PCV2) has been associated with several disease complexes, including reproductive failure. The aim of this study was to identify the subtypes of PCV2 that are associated with reproductive failure in pigs from the State of São Paulo, Brazil and to investigate co-infections with other infectious organisms. Findings: Samples of 168 aborted foetuses or mummified foetuses from five farrow-to-finish swine farms known to be infected with PCV2 and located in the State of São Paulo were tested for PCV2 by polymerase chain reaction (PCR). Positive samples were additionally tested for porcine parvovirus (PPV), Leptospira spp. and Brucella spp. by PCR. PCV2 was detected in 18 of the samples (10.7%). PPV, Brucella spp. and Leptospira spp were found in 2, 10 and 0 cases, respectively. Eleven PCV2 strains were sequenced and determined to be either genotype 2a (n = 1) or 2b (n = 10). The findings indicate that the frequency of PCV2 infections in aborted porcine foetuses from the State of São Paulo is rather low (10.7%) and that co-infection with other pathogens is common and may be involved in PCV2 associated reproductive failure. No repeatable, characteristic amino acid motifs for regions of the PCV2 capsid protein seemed to be associated with abortion in sows.
Output: Detection of porcine circovirus genotypes 2a and 2b in aborted foetuses from infected swine herds in the State of São Paulo, Brazil
A prospective study was carried out on 845 heifer calves born during 1991 on 30 Holstein dairy farms in southeast Minnesota. The objectives of the study were to describe the epidemiology of morbidty and mortality in dairy calves from birth to 16 weeks of age (with an emphasis on respiratory disease), to examine individual calf and herd management practices as risk factors for calf morbidity and mortality, and to validate producer diagnosis of mortality. Incidence rates for all morbidity, enteritis, and pneumonia were 0.20, 0.15, and 0.10 cases per 100 calf-days at risk for the period of the study. Risk of enteritis was highest in the first 3 weeks of life, with pneumonia risk highest at 10 weeks of age. Case fatality rates averaged 11.8%, 17.9%, and 9.4% for all diagnoses, enteritis, and pneumonia, respectively. Average daily rates of gain from birth to 16 weeks Iof age differed between farms that had inadequate calf housing (0.8 kg day-') versus those with adequate calf housing (1.0 kg day-i). Approximately half of the calves in the cohort (418) had blood samples taken monthly from birth until 16 weeks of age. Of the calves sampled, only 19 c,alves showed a four-fold rise in serum titers to respiratory viruses. Sixteen calves seroconverted to BVDV, two calves to IBRV, and one calf to PI3 virus. Of 98 calves less than 10 days of age tested for adequacy of passive transfer, 35 (35.7%) had serum immunoglobulin levels of less than 800 mg dl-'. There were no significant differences in mortality or morbidity between calves that had adequate passive transfer and those that did not. The incidence of mortality was 0.08 deaths per 100 calf-days at risk; 64 calves died during the 16 months of the study. The risk of death was highest at 2 weeks of age. Enteritis was the most common cause of death (28 deaths, 44% of all deaths) followed by pneumonia (19 deaths, 30% of all deaths). Comparing producer diagnosis of mortality with necropsy results yielded sensitivities of 58.3% and 56% and specifici-* Corresponding author at: Minnesota Veterinary Hospital, 4545 Hodgson Road, Saint Paul, MN 55126, USA. Tel: -I-l-61 2-484333 1. Elsevier Science B.V. SSDl 0167.5877(95)01000-9 156 N.J. Siuula et al./ Preventiue Veterinary Medicine 27 (I 996) 155-l 71 ties of 93% and 100% for producer diagnoses of enteritis and pneumonia, respectively. The kappa statistic comparing producer diagnosis with necropsy result was 0.47. The most common pathogens isolated from calves that died of enteritis were rotavirus (five calves), and Escherichia coli (four calves). Pathogens isolated from pneumonic lungs included Pasteurella multocida (three calves), Haemophilus somnus (three calves), and Pasteurella haemolytica (one calf). Veterinary Medicine 27 (19%) 155-171 157
Output: Descriptive epidemiology of morbidity and mortality in Minnesota dairy heifer calves
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses. COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage. In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.
Output: Virus-induced exacerbations in asthma and COPD
This paper aims to study the role of gold as a hedge against inflation based on local monthly gold prices in China, India, Japan, France, the United Kingdom and the United States of America in periods ranging from 1955 to 2015. We extend the literature by using a novel approach with the nonlinear autoregressive distributed lags (NARDL) model (Shin et al., 2014) . The main advantage of this model relies on its ability to simultaneously capture the short-and long-run asymmetries through positive and negative partial sum decompositions of changes in the independent variable(s). Moreover, we rely on local gold prices instead of those from London converted into local currencies like in most of previous studies. The results show that gold is not a hedge against inflation in the long run in all cases. In the short run, gold is an inflation hedge only in the UK, USA, and India. Furthermore, there is no long-run equilibrium between gold prices and the CPI in China, India and France. This difference may be due to traditional aspects of gold and custom controls for gold trade in these countries. Our robustness check suggests that the data time-frequency does not change the specification of the NARDL model but can change conclusions regarding the role of gold as a hedge against inflation in certain countries.
Output: Is gold a hedge against inflation? New evidence from a nonlinear ARDL approach
The research reported in this article explores why consumers choose to book their travel arrangements with travel agencies in regional settings. Consumers can now access online bookings for airlines, accommodation, transportation, sightseeing tours and other related products, so why do they still go to travel agencies for reservations? This article identifies the attributes consumers seek in a travel agency or consultant and determines the relative importance of these in their selection process. The research was conducted in two stages. The first stage was a series of in-depth interviews with 10 travel agency users and three travel consultants. The second stage was a mail-out survey of 400 users of travel agencies in the Darling Downs area of Queensland, Australia. Despite its regionality, the region is a significant consumer of travel with approximately eight agencies in the city of Toowoomba alone. The in-depth interviews highlighted the need to de-emphasise two particular agency attributes, agency promotion and adequate brochure provision, from the research questions and replace these with parking and travel reward programs as factors worthy of investigation. Survey results revealed that there were 12 significant attributes impacting on consumer selection and, of these, the most important were the knowledge and experience of consultants, and the helpfulness and friendliness of consultants. Of particular note was that these attributes related to the consultant and not the agency per se. Travel reward programs were seen as the least influential in this research.
Output: Major Factors Influencing Consumer Selection of Travel Agencies
Background During each winter the hospital quality of care (QoC) in pediatric wards decreases due to a surge in pediatric infectious diseases leading to overcrowded units. Bed occupancy rates often surpass the good hospital bed management threshold of 85%, which can result in poor conditions in the workplace. This study explores how QoCscores could be improved by investing in additional beds and/or better vaccination programs against vaccine-preventable infectious diseases. Methods The Cobb-Douglas model was selected to define the improvement in QoC (%) as a function of two strategies (rotavirus vaccination coverage [%] and addition of extra hospital beds [% of existing beds]), allowing improvementisocurves to be produced. Subsequently, budget minimization was applied to determine the combination of the two strategies needed to reach a given QoC improvement at the lowest cost. Data from Jessa Hospital (Hasselt, Belgium) were chosen as an example. The annual population in the catchment area to be vaccinated was 7000 children; the winter period was 90 days with 34 pediatric beds available. Rotavirus vaccination cost per course was €118.26 and the daily cost of a pediatric bed was €436.53. The target QoC increase was fixed at 50%. The model was first built with baseline parameter values. Results The model predicted that a combination of 64% vaccine coverage and 39% extra hospital beds (& 13 extra beds) in winter would improve QoC-scores by 50% for the minimum budget allocation. Conclusion The model allows determination of the most efficient allocation of the healthcare budget between rotavirus vaccination and bed expansion for improving QoCscores during the annual epidemic winter seasons.
Output: Improving the Hospital Quality of Care during Winter Periods by Optimizing Budget Allocation Between Rotavirus Vaccination and Bed Expansion
The CPK cells derived from swine kidney were infected with the attenuated TO-163 strain of transmissible gastroenteritis (TGE) virus, and fused with uninfected Vero cells in the presence of polyethylene glycol. Repeated cocultivafion of the fused cells with uninfected Vero cells rendered the virus to grow in Vero cells. The Vero cell-adapted virus acquired the ability to infect and produce cytopathic effects in several other non-permissive cell lines of nonporcine origin. No major differences in viral polypeptides were shown between the Vero cell-adapted TO-163 strain and its parent strain by indirect immunofluorescence and Western blotting using monoclonal and polyclonal antibodies to TGE virus. Transmissible gastroenteritis (TGE) virus is a coronavirus with an envelope and positive strand RNA genome. The virion contains 3 structural proteins, i.e., peplomer (S or E 2), transmembrane (M or E 1), and nucleocapsid (N) [4] . The virus replicates predominantly in villous epithelial cells of the small intestines, and results in diarrhea in infected pigs [11, 17] . Although clinical symptoms are not clearly demonstrated, the respiratory tract and the tonsils are also susceptible to infection [3, 8, 15] . The host range of TGE virus is restricted like the other coronaviruses [16], and for the propagation of the virus, swine cell cultures are commonly used, although canine [12] and feline [6] cell cultures are less often used. An attempt was made to adapt TGE virus to Vero cells non-permissive to TGE virus infection. The CPK cells derived from swine kidney [10] were inoculated with the avirulent TO-163 strain of TGE virus [5], at a multiplicity of infection of 10, and incubated at 37 °C for 18 h. The infected cells were fused
Output: Adaptation of transmissible gastroenteritis virus to growth in non-permissive Vero cells Brief Report
Background: Standard precautions (SPs) serve as the first line of defense against exposure to blood and body fluids. The objective of this study was to explore the adherence of nurses to SPs and to identify factors influencing adherence to SPs. Methods: This study was an exploratory cross-sectional survey. A total of 339 nurses from 9 general hospitals and 3 tertiary hospitals located in 3 South Korean cities were selected. Hierarchical regression was used to examine the effects of sociodemographic, individual, and institutional factors. Results: A higher, or positive, attitude was the strongest influencing factor in adherence to SPs in the final model, followed by administrative support, hospital types, and safety climate, in descending order. These 4 variables accounted for 26.0% of the variance in adherence to SPs. Conclusions: The attitudes of nurses toward SPs is important for increasing the adherence to SP best practices. The adherence of nurses to SPs will improve if safe environments are created in different hospital types and if managerial support and administrative efforts are supportive and sustained.
Output: Factors influencing the adherence of nurses to standard precautions in South Korea hospital settings
The 3' end of the 20-kb genome of the Purdue strain of porcine transmissible gastroenteritis coronavirus (TGEV) was copied into cDNA after priming with oligo(dT) and the double-stranded product was cloned into the P&I site of the pUC9 vector. One clone of 2.0-kb contained part of the poly(A) tail and was sequenced in its entirety using the chemical method of Maxam and Gilbert. Another clone of 0.7 kb also contained part of the poly(A) tail and was sequenced in part to confirm the primary structure of the most 3' end of the genome. Two potential, nonoverlapping genes were identified within the 3'terminal 1663-base sequence from an examination of open reading frames. The first gene encodes a 382-amino acid protein of 43,426 mol wt, that is the apparent nucleocapsid protein on the basis of size, chemical properties, and amino acid sequence homology with other coronavirus nucleocapsid proteins. It is flanked on its 5' side by at least part of the matrix protein gene. The second encodes a hypothetical 78.amino acid protein of 9101 mol wt that is hydrophobic at both ends. A 3'-proximal noncoding sequence of 276 bases was also determined and a conserved stretch of 9 nucleotides near the poly(A) tail was found to be common among TGEV, the mouse hepatitis coronavirus, and the avian infectious bronchitis coronavirus. Q 1986 Academic press, I~C.
Output: Sequence Analysis of the Porcine Transmissible Gastroenteritis Coronavirus Nucleocapsid Protein Gene
The collapse of iconic, keystone populations of sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon in the Northeast Pacific is of great concern. It is thought that infectious disease may contribute to declines, but little is known about viruses endemic to Pacific salmon. Metatranscriptomic sequencing and surveillance of dead and moribund cultured Chinook salmon revealed a novel arenavirus, reovirus and nidovirus. Sequencing revealed two different arenavirus variants which each infect wild Chinook and sockeye salmon. In situ hybridisation localised arenavirus mostly to blood cells. Population surveys of >6000 wild juvenile Chinook and sockeye salmon showed divergent distributions of viruses, implying different epidemiological processes. The discovery in dead and dying farmed salmon of previously unrecognised viruses that are also widely distributed in wild salmon, emphasizes the potential role that viral disease may play in the population dynamics of wild fish stocks, and the threat that these viruses may pose to aquaculture.
Output: Endangered wild salmon infected by newly discovered viruses
Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection. Citation: Gaddi PJ, Crane MJ, Kamanaka M, Flavell RA, Yap GS, et al. (2012) IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection. PLoS ONE 7(8): e42850.
Output: IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection
Proportions of QX-like genotype infectious bronchitis virus (IBV) isolates have increased over time. Here, to better understand the epidemiology and pathogenicity of IBV in China and control the spread of infectious bronchitis (IB), we conducted sequence analyses and examined the pathogenicity of 5 field isolates from diseased flocks in 2017 and 2018. Sequence analyses revealed that all the 5 strains, as well as many recent field isolates from other researchers, belonged to the QX-like IBV genotype, which were distantly related to commercial vaccine strains. Viral pathogenicity experiments showed that the isolates caused high morbidity and severe ciliostasis in chickens, although they caused milder lethality. This provides further evidence that QX-like IBV emergence remains a major problem in the poultry industry, and information on IBV epidemiology and pathogenicity may help to control IB.
Output: Molecular characteristics and pathogenicity analysis of QX-like avian infectious bronchitis virus isolated in China in 2017 and 2018
The authors conducted a study using surveillance monitoring methodology to identify operatory contamination and to evaluate the effectiveness of infection control procedures. Viridans streptococci were evaluated as biological indicators of oral contamination. Viridans streptococci, abundant in human saliva, were detected on operatory surfaces after dental treatments were finished and surfaces were disinfected. The findings validate current concepts of infection control as demonstrated in barrier methods.
Output: OF CROSS-CONTAMINATION IN THE DENTAL OPERATORY
Live recombinant bacteria represent attractive antigen delivery systems able to induce both mucosal and systemic immune responses against heterologous antigens. The first live recombinant bacterial vectors developed were derived from attenuated pathogenic microorganisms. In addition to the difficulties often encountered in the construction of stable attenuated mutants of pathogenic organisms, attenuated pathogens may retain a residual virulence level that renders them unsuitable for the vaccination of partially immunocompetent individuals such as infants, the elderly or immunocompromised patients. As an alternative to this strategy, non-pathogenic food-grade lactic acid bacteria (LAB) maybe used as live antigen carriers. This article reviews LAB vaccines constructed using antigens other than tetanus toxin fragment C, against bacterial, viral, and parasitic infective agents, for which protection studies have been performed. The antigens utilized for the development of LAB vaccines are briefly described, along with the efficiency of these systems in protection studies. Moreover, the key factors affecting the performance of these systems are highlighted.
Output: Development of Vaccine Delivery Vehicles Based on Lactic Acid Bacteria
Flies are known to be mechanical vectors of bacterial, viral, and parasitic diseases. Although flies are known to transmit disease, the effects of cleaning behavior have not been well studied. This study quantified the cleaning effectiveness and behavior of three fly species: Sarcophaga bullata, Musca domestica L., and Drosophila virilis. Flies were transferred to plates of Escherichia coli or Pseudomonas aeruginosa and allowed to walk on the bacteria for a total of 5 min. After the flies were contaminated, they were either immediately collected to quantify bacteria or were placed onto sterile plates to clean for 5 or 10 min. After cleaning, flies were placed into tubes with 1 ml of sterile 0.85% saline and were gently shaken for 1 min to remove bacteria. A serial dilution was made and 50-ml spot titers were plated. Cleaning behavior was also monitored and scored for a period of 5 min. Results demonstrate a bacterial reduction for both bacteria on all three fly species. Sarcophaga bullata and D. virilis both showed a significant reduction of both bacteria within 10 min, whereas M. domestica only showed a significant reduction in P. aeruginosa. Cleaning behavior increased significantly in flies that were exposed to bacteria compared to flies that were not exposed to bacteria. This study is important, as it demonstrates that fly cleaning could affect mechanical transmission of disease, and additional studies should look at flies' abilities to remove other types of microorganisms.
Output: Role of Fly Cleaning Behavior on Carriage of Escherichia coli and Pseudomonas aeruginosa
Extracellular vesicles (EVs) are thought to be important in cell-cell communication and have elicited extraordinary interest as potential biomarkers of disease. However, quantitative methods to enable elucidation of mechanisms underlying release are few. Here, we describe a cell-based assay for monitoring EV release using the EV-enriched tetraspanin CD63 fused to the small, ATP-independent reporter enzyme, Nanoluciferase. Release of CD63-containing EVs from stably expressing cell lines was monitored by comparing luciferase activity in culture media to that remaining in cells. HEK293, U2OS, U87 and SKMel28 cells released 0.3%-0.6% of total cellular CD63 in the form of EVs over 5 hrs, varying by cell line. To identify cellular machinery important for secretion of CD63-containing EVs, we performed a screen of biologically active chemicals in HEK293 cells. While a majority of compounds did not significantly affect EV release, treating cells with the plecomacrolides bafilomycin or concanamycin, known to inhibit the V-ATPase, dramatically increased EV release. Interestingly, alkalization of the endosomal lumen using weak bases had no effect, suggesting a pH-independent enhancement of EV release by V-ATPase inhibitors. The ability to quantify EVs in small samples will enable future detailed studies of release kinetics as well as further chemical and genetic screening to define pathways involved in EV secretion.
Output: A cell-based assay for CD63-containing extracellular vesicles
Multilateral agencies define and operationalized health and development in a variety of ways. The World Health Organization (WHO) and the World Bank are two dominant actors in health and development. Each espouses a different ideal of health as it relates to the process of development. The WHO defines health as a human right, and focuses on health outcomes as inputs to and the result of development. The World Bank's approach to development focuses largely on macro-economic growth as input to human capabilities. The World Bank became a leading actor in international health policy in the 1990s when it operationalized health as an outcome of financial and health care systems. This chapter looks at programming efforts by the WHO and the World Bank to foster development via investment in health or through macro-economic adjustment. Results are mixed. Efforts to improve primary care were successful in improving health outcomes of children under five, but made little impact on maternal mortality. Structural adjustment programs achieved moderate success with medium-to long-term economic growth but increased health inequities. These mixed achievements resulted in an effort by the United Nations to foster a multi-sectoral approach to development espoused in the Millennium Development Goals and Sustainable Development Goals.
Output: International Organizations and Their Approaches to Fostering Development
Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.
Output: Subviral Particle as Vaccine and Vaccine Platform
The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M pro s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M pro -inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structureassisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M pro s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases. Citation: Yang H, Xie W, Xue X, Yang K, Ma J, et al. (2005) Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS Biol 3(10): e324.
Output: Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases
In the drylands of Africa, pastoralists have been facing new challenges, including those related to environmental shocks and stresses. In northern Kenya, under conditions of reduced rainfall and more frequent droughts, one response has been for pastoralists to focus increasingly on camel herding. Camels have started to be kept at higher altitudes and by people who rarely kept camels before. The development has been understood as a climate change adaptation strategy and as a means to improve climate resilience. Since 2003, development organizations have started to further the trend by distributing camels in the region. Up to now, little has been known about the nature of, reasons for, or ramifications of the increased reliance on camels. The paper addresses these questions and concludes that camels improve resilience in this dryland region, but only under certain climate change scenarios, and only for some groups.
Output: Camels and Climate Resilience: Adaptation in Northern Kenya
With respect to the asymptomatic transmission characteristics of the novel coronavirus that appeared in 2019 (COVID-19), a susceptible-asymptomatic-infected-recovered-death (SAIRD) model that considered human mobility was constructed in this study. The dissemination of COVID-19 was simulated using computational experiments to identify the mechanisms underlying the impact of city and residential lockdowns on controlling the spread of the epidemic. Results: The implementation of measures to lock down cities led to higher mortality rates in these cities, due to reduced mobility. Moreover, implementing city lockdown along with addition of hospital beds led to improved cure and reduced mortality rates. Stringent implementation and early lockdown of residential units effectively controlled the spread of the epidemic, and reduced the number of hospital bed requirements. Collectively, measures to lock down cities and residential units should be taken to prevent the spread of COVID-19. In addition, medical resources should be increased in cities under lockdown. Implementation of these measures would reduce the spread of the virus to other cities and allow appropriate treatment of patients in cities under lockdown.
Output: Impact of city and residential unit lockdowns on prevention and control of COVID-19
Background: Intestinal infectious diseases (IIDs) have caused numerous deaths worldwide, particularly among children. In China, eight IIDs are listed as notifiable infectious diseases, including cholera, poliomyelitis, dysentery, typhoid and paratyphoid (TAP), viral Hepatitis A, viral Hepatitis E, hand-foot-mouth disease (HFMD) and other infectious diarrhoeal diseases (OIDDs). The aim of the study is to analyse the spatio-temporal distribution of IIDs from 2006 to 2016. Methods: Data on the incidence of IIDs from 2006 to 2016 were collected from the public health science data centre issued by the Chinese Center for Disease Control and Prevention. This study applied seasonal decomposition analysis, spatial autocorrelation analysis and space-time scan analysis. Plots and maps were constructed to visualize the spatio-temporal distribution of IIDs. Results: Regarding temporal analysis, the incidence of HFMD and Hepatitis E showed a distinct increasing trend, while the incidence of TAP, dysentery, and Hepatitis A presented decreasing trends over the last decade. The incidence of OIID remained steady. Summer is the season with the greatest number of cases of different IIDs. Regarding the spatial distribution, approximately all p values for the global Moran's I from 2006 to 2016 were less than 0.05, indicating that the incidences of the epidemics were unevenly distributed throughout the country. The high-risk areas for HFMD and OIDD were located in the Beijing-Tianjin-Tangshan (BTT) region and south China. The high-risk areas for TAP were located in some parts of southwest China. A higher incidence rates for dysentery and Hepatitis A were observed in the BTT region and some west provincial units. The high-risk areas for Hepatitis E were the BTT region and the Yangtze River Delta area. Conclusions: Based on our temporal and spatial analysis of IIDs, we identified the high-risk periods and clusters of regions for the diseases. HFMD and OIDD exhibited high incidence rates, which reflected the negligence of Class C diseases by the government. At the same time, the incidence rate of Hepatitis E gradually surpassed Hepatitis A. The authorities should pay more attention to Class C diseases and Hepatitis E. Regardless of the various distribution patterns of IIDs, disease-specific, location-specific, and disease-combined interventions should be established.
Output: A descriptive analysis of the Spatio- temporal distribution of intestinal infectious diseases in China
Background: The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. For poultry, an overall prevalence of 41 % of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. For hunting: All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. For cooking: Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.
Output: Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala
IFNb innate immune plays an essential role in antiviral immune. Previous reports suggested that many important regulatory proteins in innate immune pathway may be modified by ubiquitin and that many de-ubiquitination (DUB) proteins may affect immunity. Monocyte chemotactic protein-inducing protein 1 (MCPIP1), one of the CCCH Zn finger-containing proteins, was reported to have DUB function, but its effect on IFNb innate immune was not fully understood. In this study, we uncovered a novel mechanism that may explain how MCPIP1 efficiently inhibits IFNb innate immune. It was found that MCPIP1 negatively regulates the IFNb expression activated by RIG-I, STING, TBK1, IRF3. Furthermore, MCPIP1 inhibits the nuclear translocation of IRF3 upon stimulation with virus, which plays a key role in type I IFN expression. Additionally, MCPIP1 interacts with important modulators of IFNb expression pathway including IPS1, TRAF3, TBK1 and IKKε. Meanwhile, the interaction between the components in TRAF3-TBK1-IKKε complex was disrupted by MCPIP1. These results collectively suggest MCPIP1 as an innate immune regulator encoded by the host and point to a new mechanism through which MCPIP1 negatively regulates IRF3 activation and type I IFNb expression.
Output: MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex
Background: Hajj is the world's largest annual mass gathering that attracts two to three million Muslims from around the globe to a religious assemblage in Makkah, Saudi Arabia. The risk of acquisition and transmission of influenza among Hajj pilgrims is high. Therefore, influenza vaccination is recommended, and was monitored frequently among pilgrims from different countries. However, the vaccination uptake among Saudi pilgrims has not been assessed in recent years. Objective: This analysis aims to evaluate influenza vaccine uptake among Saudi Hajj pilgrims, and identify the key barriers to vaccination. Method: Data on influenza vaccination were obtained from Saudi pilgrims who took part in a large trial during the Hajj of 2013, 2014 and 2015. Pilgrims were met and recruited in Mina, Makkah during the peak period of Hajj and were asked to complete a baseline questionnaire that recorded their influenza vaccination history, including reason(s) for non-receipt of vaccine. Results: A total of 6974 Saudi pilgrims aged between 18 and 95 (median 34) years were recruited; male to female ratio was 1:1.2. Of the total, 90.8% declared their influenza vaccination history, 51.3% of them reported receiving influenza vaccine before travel to Hajj. The vaccination rates for the years 2013, 2014 and 2015 were 21.4%, 48.2% and 58.1%, respectively (P < 0.001). Of 1,269 pilgrims who were at higher risk of severe disease, 54.5% received the vaccine. Lack of awareness (47.5%), reliance on natural immunity (15.8%) and being busy (15.5%) were the main reasons for non-receipt. Conclusion: These data from a convenience sample indicate that influenza vaccine uptake among Saudi Hajj pilgrims is increasing over years but still needs further improvement. Lack of awareness and misperceptions are the main barriers. Education of Saudi pilgrims and health professionals is required to raise awareness about influenza vaccination. Further studies are needed to understand pilgrims' misperceptions.
Output: Influenza vaccination among Saudi Hajj pilgrims: Revealing the uptake and vaccination barriers
Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of b-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus. Citation: Wang J, Fang S, Xiao H, Chen B, Tam JP, et al. (2009) Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with b-Actin and Its Implication in Virion Assembly and Budding. PLoS ONE 4(3): e4908.
Output: Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with b-Actin and Its Implication in Virion Assembly and Budding