niryuu/sni-each-converted huggingface dataset:
Background: It is unknown to what extent the human coronaviruses (HCoVs) OC43, HKU1, 229E and NL63 infect healthy children. Frequencies of infections are only known for hospitalized children. Objectives: Comparing infection frequencies in children who have mild infections with frequencies in children needing hospital uptake will determine whether infection by one of the four HCoVs leads to more severe disease. In addition, the sequence of seroconversions can reveal whether infection by one HCoV protects from infection by other HCoVs. Study design: Two distinct study groups were monitored: healthy children and children hospitalized due to respiratory infection. HCoV natural infection rates in healthy children were obtained by serology in 25 newborns (followed 0-20 months). The frequencies of severe HCoVs infection was determined by real time RT-PCR among 1471 hospitalized infants (<2-years old) with acute respiratory tract disease. Results: The majority of healthy children seroconverted for HCoV-OC43 (n = 19) and HCoV-NL63 (n = 17), less for HCoV-HKU1 (n = 9) and HCoV-229E (n = 5). Notably, HCoV-HKU1 seroconversion was absent after HCoV-OC43 infection. Also HCoV-229E infection was rarely observed after HCoV-NL63 infection (1 out of 5). In the hospital 207 (14%) out of 1471 children were HCoV positive. Again we observed most infection by HCoV-OC43 (n = 85) and HCoV-NL63 (n = 60), followed by HCoV-HKU1 (n = 47) and HCoV-229E (n = 15). Conclusions: HCoV-NL63 and HCoV-OC43 infections occur frequently in early childhood, more often than HCoV-HKU1 or HCoV-229E infections. HCoV-OC43 and HCoV-NL63 may elicit immunity that protects from subsequent HCoV-HKU1 and HCoV-229E infection, respectively, which would explain why HCoV-OC43 and HCoV-NL63 are the most frequently infecting HCoVs. There are no indications that infection by one of the HCoVs is more pathogenic than others. Crown
Output: The dominance of human coronavirus OC43 and NL63 infections in infants
Objective To describe how pandemic influenza A(H1N1)2009 [A (H1N1)pdm09] activity varied during the We calculated weekly proportions of A(H1N1)pdm09-positive specimens out of all A(H1N1)pdm09-positive specimens detected during the study period for each country. We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09 weekly proportion [peak activity], number of weeks between the 5th and 95th percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity]) between countries in temperate and tropical-subtropical regions. We quantified the proportion of A (H1N1)pdm09 out of all influenza A specimens by country and correlated it with countries' central latitudes. Results We analyzed data from 80 countries (47 temperate, 33 tropical-subtropical). The median proportion of cases identified during the peak week was higher in temperate (0Á12) than in tropical-subtropical (0Á09) regions (P < 0Á01). The median duration of activity was longer in tropical-subtropical (27 weeks) than in temperate countries (20 weeks) (P < 0Á01). In most temperate countries (98%), peak pandemic activity occurred during the fall-winter period. There was a positive correlation between country central latitude and proportion of A(H1N1)pdm09 out of all influenza A specimens (r: 0Á76; P < 0Á01). Conclusions The transmission of A(H1N1)pdm09 exhibited similarities with seasonal influenza transmission in that activity varied between temperate and tropical-subtropical countries and by time of year. Our findings suggest the potential utility of accounting for these factors during future pandemic planning. Keywords 2009 influenza A (H1N1), pandemic influenza, seasonality. Please cite this paper as: Storms et al. (2013) Worldwide transmission and seasonal variation of pandemic influenza A(H1N1)2009 virus activity during the
Output: Global Influenza Programme, World Health Organization
To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1-2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.
Output: Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease
Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophilinduced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment. (J Allergy Clin Immunol 2015;136:838-47.) 
Output: Neutrophils in respiratory syncytial virus infection: A target for asthma prevention
Cox, E., Pensaert, M.B., Callebaut, P. and van Deun, K., 1990. Intestinal replication of a porcine respiratory coronavirus closely related antigenically to transmissible gastroenteritis virus. Vet. Microbiol., One-week-old piglets were inoculated with the porcine respiratory coronavirus (PRCV) either intravenously or directly into the lumen of the gastrointestinal tract. Both inoculation routes resulted in the isolation of virus from the caudal small intestine. Viral replication, however, was only observed upon inoculation into the digestive tract in quantities of > 10 3 TCIDso. Replication remained limited to a few unidentified cells located in or underneath the epithelial layer at villus-or crypt-sites. Virus was excreted in the faeces for several days but infection of the respiratory tract occurred rarely in the same pigs. The results of this study indicate that small changes in molecular structure between PRCV and transmissible gastroenteritis virus have resulted in important changes in host cell tropism.
Output: Intestinal replication of a porcine respiratory coronavirus closely related antigenically to the enteric transmissible gastroenteritis virus
African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibition on viral production. Caspases 3, 9 and 12 were activated from 16 h post-infection, but not caspase 8. Indeed, caspase 3 activation during the early stages of the infection appeared to be crucial for efficient virus exit. In addition, the inhibition of membrane blebbing reduced the release of virus particles from the cell. ASFV uses the endoplasmic reticulum (ER) as a site of replication and this process can trigger ER stress and the unfolded protein response (UPR) of the host cell. In addition to caspase 12 activation, indicators of ER stress include the upregulation of the chaperones calnexin and calreticulin upon virus infection. Moreover, ASFV induces transcription factor 6 signaling pathway of the UPR, but not the protein kinase-like ER kinase or the inositol-requiring enzyme 1 pathways. Thus, the capacity of ASFV to regulate the UPR may prevent early apoptosis and ensure viral replication.
Output: The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection
C57 strain mice were inoculated intraperitoneally with denatured mouse hepatitis virus strain 3 particles and virus surface projection, membrane and ribonucleoprotein subeomponents, obtained from detergent treated purified virus preparations. All immunised animals developed high levels of serum antibody directed against the respective antigens, detectable by enzyme-linked immunosorbent assay. Mice that had been immunised with denatured virus particles or surface projections were protected against infection with mouse hepatitis virus strain 3, whereas immunisation with virus membrane or ribonucleoprotein subcomponents failed to protect mice against virus challenge.
Output: Archives of Virology Antigenieity of Mouse Hepatitis Virus Strain 3 Subeomponents in C57 Strain Miee
a b s t r a c t Cyclophilin A (CyPA) is a peptidyl-prolyl cis/trans isomerase originally identified as the target of the immunosuppressive drug cyclosporine A. A number of reports have demonstrated that CyPA plays a critical role in the successful replication of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), etc. However, recent studies demonstrated that CyPA also possesses a repressive effect on the replication of some viruses like Influenza A virus and rotavirus. Moreover, CyPA could also regulate host IFN-I response to viral infections. Together, these evidences showed diverse roles of CyPA in viral infection.
Output: Cyclophilin A and viral infections
The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the "real life" situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model "crowding agents". Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of OPEN ACCESS Int. J. Mol. Sci. 2014, 15 23091 macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.
Output: What Macromolecular Crowding Can Do to a Protein
This research reports the design, analysis, integration, and test of a prototype of a real-time convective polymerase chain reaction (RT-cPCR) machine that uses a color charged coupled device (CCD) for detecting the emission of fluorescence intensity from an RT-cPCR mix in a microliter volume glass capillary. Because of its simple mechanism, DNA amplification involves employing the cPCR technique with no need for thermocycling control. The flow pattern and temperature distribution can greatly affect the cPCR process in the capillary tube, a computational fluid dynamics (CFD) simulation was conducted in this study for the first time to estimate the required period of an RT-cPCR cycle. This study also tested the PCR mix containing hepatitis B virus (HBV) plasmid samples by using SYBR Green I fluorescence labeling dye to assess the prototype performance. The measured results from the image-processing scheme indicate that the RT-cPCR prototype with a CCD-based fluorometer can achieve similar DNA quantification reproducibility compared to commercial machines, even when the initial DNA concentration in the test PCR mix is reduced to 10 copies/L
Output: A real-time convective PCR machine in a capillary tube instrumented with a CCD-based fluorometer
A total of 1002 patients were recruited and 892 were enrolled (110 were excluded based on pre-determined exclusion criteria). Based on the reference standard process described in the 'Methods' section, patients were assigned to four different diagnosis groups: (i) bacterial; (ii) viral; (iii) no apparent infectious disease or healthy (controls); and (iv) indeterminate. Patients diagnosed by the panel as having mixed infections (bacteria plus virus) were labeled as bacterial because they are managed similarly (e.g. treated with antibiotics) (see 'Methods', Fig. 1A ). In total, 89% of all enrolled patients were assigned a diagnosis, a rate which approaches the literature-documented limit [1-3]. The following sections provide a detailed description of patient characteristics, which includes all the patients with a final diagnosis (n=794): 765 patients included in the study cohort and 29 patients for which the serum samples were depleted during the screening phase (Fig. 1).  Patients of all ages were recruited to the study. The patients with agreed diagnosis (diagnosed patients; n=794) included more pediatric (≤18 years) than adult (>18 years) patients (445 patients [56%] vs 349 [44%]). The age distribution was relatively uniform for patients aged 20-80 years and peaked at <4 years of age for pediatric patients (Fig.  S2) . The observed age distribution for pediatric patients is consistent with that expected and represents the background distribution in the inpatient setting [4] (e.g., the emergency department [ED], pediatrics departments, and internal departments). Patients of both genders were recruited to the study. The patient population was balanced in respect to gender distribution (47% females, 53% males).
Output: 3. Supporting Information S3 -Cohort characteristics 3.1. Summary of the patient cohorts used in this study
Background: Porcine epidemic diarrhea (PED) is a lethal infectious disease in suckling piglets with symptoms including watery diarrhea caused by PED virus (PEDV). Since the late 1990's, live vaccines based on genogroup 1 virus have been used in Japan, and a significant amount of the vaccine has been used even after new genogroups invaded in 2013. In this study, we evaluated the effect of a conventional PED live vaccine on a newly prevalent genogroup 2 field strain in experimental and field situations. Methods: Two pregnant sows were administered twice the live vaccine before farrowing. A pregnant sow was served as a negative control. All newborn piglets were challenged with the genogroup 2 virus, and clinical signs were monitored for 7 days post challenge. PEDV-specific immune responses in serum and milk of the sows were assayed by virus neutralization assay. The efficacy of PED live vaccine in vaccinated or non-vaccinated farms was evaluated by comparing the mortality rate of suckling piglets after the onset of PED. Results: The challenged piglets exhibited watery diarrhea with or without vaccination. However, the clinical score of piglets born from vaccinated sows significantly improved after the 4th day of the challenge. The survival rate of piglets in the vaccinated group at the end of the experimental period was 80%, whereas in the control group was 0%. Neutralizing antibody titers in serum and milk of control sow was negative throughout the experimental period, whereas high titers were observed in the vaccinated sows. The vaccinated farms significantly reduced the mortality rate of suckling piglets after the onset of PED, compared to farms not vaccinated. Conclusions: The conventional PED live vaccine induced the lactogenic immunity to vaccinated sows and showed partial protection against the genogroup 2 virus both under the experimental and field conditions.
Output: Efficacy of genogroup 1 based porcine epidemic diarrhea live vaccine against genogroup 2 field strain in Japan
The explosive pace of sequencing of RNA viruses is leading to rapid advances in our understanding of the evolution of these viruses and of the ways in which their genomes are organized and expressed. New insights are coming not only from genomic nucleotide sequence comparisons, but also from direct sequencing of transcribed mRNAs and of RNAs that serve as intermediates in replication. BSMV--barley stripe mosaic virus; L--large; Ldr~leader RNA; M~medium; NDV--Newcastle disease virus; NTR--non-translated region; ORF~open reading frame; PIV--parainfluenza virus; S~small; ssRNA--single-strand RNA; SVS~simian virus 5; TMV--tobacco mosaic virus; vc RNA--virus complementary RNA.
Output: RNA viruses: genome structure and evolution
The main objective of this brief communication is to inform about the exposure to certain pathogens of interest for mesocarnivores in wildcats (Felis silvestris silvestris) that inhabit a human-domestic-wild ecotone located in a Natural Park (Serranía de Cuenca, Central Spain). Blood and mucosal swabs (nasal, conjunctival and rectal) samples were collected from nine alive animals to detect canine distemper virus (CDV), parvovirus (CPV/FPV), feline leukaemia virus (FeLV), feline coronavirus (FCoV), feline immunodeficiency virus (FIV), Leptospira interrogans, Chlamydia felis, Ehrlichia canis, Toxoplasma gondii, and Neospora caninum. ELISA, immunochromatograpy, microscopy agglutination test and PCR assays were used. The results show the first worldwide detection of exposure of wildcats to L. interrogans (3 positive/9 analysed) and the first detection of exposure to CVD (7/9), of carriers of C. felis (2/9) and of fecal spreading of CPV-FPV (2/9) in wildcats in Spain. Exposure to T. gondii and CPV-FPV was detected in 5 of the 9 wildcats analysed, and to FelV in 4 of 9. No FIV, FCoV, Ehrlichia canis and Neospora caninum were detected. The results reveal the circulation of pathogens among the wildcat population studied, but more vigilance is needed for an accurate assessment of the impact of these pathogens on the health status of this population.
Output: Canine distemper virus may affect European wild cat populations in Central Spain
Developed over the past two decades, the antisense strategy has become a technology of recognised therapeutic potential, and many of the problems raised earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cells remains an important and inordinately difficult challenge. Synthetic polymers appeared on this scene in the middle 1980s, and there is a surprisingly large variety used or proposed so far as agents for delivery of oligodeoxynucleotides. After discussing the principles of antisense strategy, certain aspects of the ingestion of macromolecules by cells, and the present situation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and/or cell membrane permeabilisation agents for delivery of antisense oligodeoxynucleotides. Structural aspects of various polymers, as well as the results, promises and limitations of their use are critically evaluated. r
Output: The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides
Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-β to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-β. Viral load and immune responses of immunized mice were analyzed over time. Our results indicate that the RV expressing IFN-β (IFN(+)) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-β reduces viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN(+) RV had a significantly greater number of activated CD8+ T cells. The increased activation of CD8 + T cells was dependent on IFN-β signaling, as we saw no difference following infection of IFNAR −/− mice. Although mice immunized with IFN(+) have a greater primary immune response than controls, immunized mice that were challenged with vaccinia expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-β, even with greatly reduced viral replication, indicates the beneficial effect of IFN-β for the host.
Output: Interferon-β expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity
Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression. At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells. Efferent fibers identified by peripherin or calcitonin gene-related protein do not coexpress alpha7GFP. In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus. Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.
Output: The expression of nicotinic receptor alpha7 during cochlear development
Cellular membranes display an incredibly diverse range of shapes, both in the plasma membrane and at membrane bound organelles. These morphologies are intricately related to cellular functions, enabling and regulating fundamental membrane processes. However, the biophysical mechanisms at the origin of these complex geometries are not fully understood from the standpoint of membrane-protein coupling. In this work, we focused on a minimal model of helicoidal ramps representative of specialized endoplasmic reticulum compartments. Given a helicoidal membrane geometry, we asked what is the distribution of spontaneous curvature required to maintain this shape at mechanical equilibrium? Based on the Helfrich energy of elastic membranes with spontaneous curvature, we derived the shape equation for minimal surfaces, and applied it to helicoids. We showed the existence of switches in the sign of the spontaneous curvature associated with geometric variations of the membrane structures. Furthermore, for a prescribed gradient of spontaneous curvature along the exterior boundaries, we identified configurations of the helicoidal ramps that are confined between two infinitely large energy barriers. Overall our results suggest possible mechanisms for geometric control of helicoidal ramps in membrane organelles based on curvatureinducing proteins.
Output: Geometric coupling of helicoidal ramps and curvature-inducing proteins in organelle membranes
Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the "magic bullet" has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1-2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use.
Output: Therapeutic Antibodies: Current State and Future Trends -Is a Paradigm Change Coming Soon?
Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than precommitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.
Output: The Acute Environment, Rather than T Cell Subset Pre- Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease's pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention. Author Contributions: Conceptualization, P.S., E.B.; Data curation, P.S., P.L.M., D.B., T.M.M.; Funding acquisition, P.S.; Investigation, P.S., P.L.M., E.B., T.M.M.; Writing-review and editing, P.S., P.L.M., D.B., E.B., T.M.M., E.C., N.B., F.F., M.T., M.S.
Output: Molecular Sciences The Role of the Lung's Microbiome in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis
A majority of the world's population will live in urban areas by 2007 and cities are exerting growing influence on the health of both urban and non-urban residents. Although there long has been substantial interest in the associations between city living and health, relatively little work has tried to understand how and why cities affect population health. This reflects both the number and complexity of determinants and of the absence of a unified framework that integrates the multiple factors that influence the health of urban populations. This paper presents a conceptual framework for studying how urban living affects population health. The framework rests on the assumption that urban populations are defined by size, density, diversity, and complexity, and that health in urban populations is a function of living conditions that are in turn shaped by municipal determinants and global and national trends. The framework builds on previous urban health research and incorporates multiple determinants at different levels. It is intended to serve as a model to guide public health research and intervention. r
Output: Cities and population health
Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.
Output: Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa
Lymphoid chemokines play an essential role in the establishment and maintenance of lymphoid tissue microarchitecture and have been implicated in the formation of tertiary (or ectopic) lymphoid tissue in chronic inflammatory conditions. Here, we review recent advances in lymphoid chemokine research in central nervous system inflammation, focusing on multiple sclerosis and the animal model experimental autoimmune encephalomyelitis. We also highlight how the study of lymphoid chemokines, particularly CXCL13, has led to the identification of intrameningeal B-cell follicles in the multiple sclerosis brain paving the way to the discovery that these abnormal structures are highly enriched in Epstein-Barr virus-infected B cells and plasma cells.
Output: Lymphoid chemokines in chronic neuroinflammation
Feline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats and is associated with interstitial pneumonia, oral ulceration and polyarthritis. Recently, outbreaks have involved a highly virulent FCV that leads to multisystemic signs. Virus isolation and conventional RT-PCR are the most common methods used for FCV diagnosis. However, real-time RT-PCR offers a rapid, sensitive, specific and easy tool for nucleic acid detection. The objective of this study was to design a TaqMan probe-based, real-time RT-PCR assay for detection of FCV. It was determined in our previous study that the first 120 nucleotides of the 5 0 region of the genome are highly conserved among FCV isolates. Primers and a probe specific for this region were designed for a real-time RT-PCR assay to detect FCV. Initial validation was done using 15 genetically diverse isolates. Also, 122 samples were tested by the new assay and virus isolation. The real-time RT-PCR assay was as sensitive and specific as virus isolation and was far more rapid. This real-time RT-PCR assay targeting the conserved 5 0 region of the genome is a fast, economical and accurate method for detection of FCV.
Output: Development and validation of a TaqMan real-time reverse transcription-PCR for rapid detection of feline calicivirus
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.
Output: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding
Chloroquine (CQ) and its hydroxyl analogue hydroxychloroquine (HCQ) are weak bases with a half-century long use as antimalarial agents. Apart from this antimalarial activity, CQ and HCQ have gained interest in the field of other infectious diseases. One of the most interesting mechanisms of action is that CQ leads to alkalinisation of acid vesicles that inhibit the growth of several intracellular bacteria and fungi. The proof of concept of this effect was first used to restore intracellular pH allowing antibiotic efficacy for Coxiella burnetii, the agent of Q fever, and doxycycline plus HCQ is now the reference treatment for chronic Q fever. There is also strong evidence of a similar effect in vitro against Tropheryma whipplei, the agent of Whipple's disease, and a clinical trial is in progress. Other bacteria and fungi multiply in an acidic environment and encouraging in vitro data suggest that this concept may be generalised for all intracellular organisms that multiply in an acidic environment. For viruses, CQ led to inhibition of uncoating and/or alteration of post-translational modifications of newly synthesised proteins, especially inhibition of glycosylation. These effects have been well described in vitro for many viruses, with human immunodeficiency virus (HIV) being the most studied. Preliminary in vivo clinical trials suggest that CQ alone or in combination with antiretroviral drugs might represent an interesting way to treat HIV infection. In conclusion, our review re-emphasises the paradigm that activities mediated by lysosomotropic agents may offer an interesting weapon to face present and future infectious diseases worldwide.
Output: Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century
Objective. To understand the causes and transmission routes of, as well as risk factors, for a Salmonella outbreak in a tour group. Method. A retrospective cohort design was used to conduct an epidemiological field investigation. Real-time fluorescent quantitative PCR, bacterial culture, and serological identification methods were used for pathogen detection and identification. Result. ere were 7 cases of illness, and the attack rate was 46.67%. e onset date was concentrated on May 9 and 10. All cases were found in the tour group, and no cases occurred in the nontour group. e results of this retrospective cohort study showed that the consumption of boiled eggs for breakfast on May 9 was a common factor (R 2 � 6.67, P � 0.023). Salmonella enteritidis was identified from the patients' stool and vomit. Conclusion. e food poisoning epidemic was caused by Salmonella enteritidis. In the summer and autumn, attention should be paid to preservation, processing, and cooking of food to avoid bacterial contamination. To prevent sickness, travelers should know the disease prevalence at their destinations in advance.
Output: Survey of Traveler's Diarrhea: Epidemiology and Testing Reveal the Source
Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle.
Output: Codon adaptation biases among sylvatic and urban genotypes of Dengue virus type 2
The indirect immunoperoxidase (IIP) assay was compared with the reverse transcription-polymerase chain reaction (RT-PCR) for detection of 793/B serotype of infectious bronchitis virus in tissues samples collected from experimentally infected chickens. This technique was optimized in specific pathogen-free (SPF)-embryonated chicken eggs and broiler chickens inoculated with the Iranian IR/773/2001 strain of 793/B serotype The trachea, lung, kidney, and cecal tonsil tissue samples from experimentally infected chicken embryos and chickens were collected in order to prepare tissue sections in IIP assay and to detect in RT-PCR. The sensitivity and specificity values of IIP assay were, respectively, 83 and 84 %, and the positive and negative prediction values were 71 and 91 % when compared with RT-PCR.
Output: Detection of 793/B serotype of infectious bronchitis virus in tissue sample by indirect immunoperoxidase assay
Microglia and macrophages are related cell types that play an important role in the pathogenesis of MS and EAE. This chapters reviews the role of these cells in the normal brain and their contribution to inflammatory demyelinating disease, including their role in antigen presentation, co-stimulation, and production of cytokines and other inflammatory mediators The microglia, a brain-resident, non-neuronal cell and the blood-derived or haematogenous macrophage represent two related cell types involved in key events in the development of pathology in Multiple Sclerosis and its autoimmune animal model, the Experimental Allergic Encephalomyelitis. Microglia and macrophages fulfil a variety of different functions, but they are also recognized for their ability to act as a particularly fine sensor of brain pathology. Both cell types are rapidly activated and recruited to sites of infection, neurodegeneration, stroke, autoimmune inflammatory models such as EAE and its presumptive human counterpart, multiple sclerosis. Microglia and macrophages are stimulated by a variety of cytokines, neurotransmitters, modulators and putative neurotoxins, extracellular matrix molecules and proteases present in the inflamed central nervous system. Moreover, both cell types are plastic in their morphology and cellular identity. The presence of dying cells and cell debris will cause a transformation of phagocytic microglia into a detached, rounded and migratory or amoeba-like (amoeboid) macrophage (Streit et al., 1988; Bohatschek et al., 2001). This also works in reverse: surrounded by a CNS environment, non-phagocytic macrophages freshly recruited from the blood stream will gradually develop
Output: Chapter A7 ROLE OF MICROGLIA AND MACROPHAGES IN EAE
Emerging diseases are increasing burdens on public health, negatively affecting the world economy, causing extinction of species, and disrupting ecological integrity. One Health recognizes that human, domestic animal, and wildlife health are interconnected within ecosystem health and provides a framework for the development of multidisciplinary solutions to global health challenges. To date, most health-promoting interventions have focused largely on single-sector outcomes. For example, risk for transmission of zoonotic pathogens from bush-meat hunting is primarily focused on human hygiene and personal protection. However, bush-meat hunting is a complex issue promoting the need for holistic strategies to reduce transmission of zoonotic disease while addressing food security and wildlife conservation issues. Temporal and spatial separation of humans and wildlife, risk communication, and other preventative strategies should allow wildlife and humans to co-exist. Upstream surveillance, vaccination, and other tools to prevent pathogen spillover are also needed. Clear multi-sector outcomes should be defined, and a systems-based approach is needed to develop interventions that reduce risks and balance the needs of humans, wildlife, and the environment. The ultimate goal is long-term action to reduce forces driving emerging diseases and provide interdisciplinary scientific approaches to management of risks, thereby achieving optimal outcomes for human, animal, and environmental health.
Output: Optimization of human, animal, and environmental health by using the One Health approach
Background: Swine-origin virus infection spreading widely could cause significant economic loss to porcine industry. Novel antiviral agents need to be developed to control this situation. Methods: In this study, we evaluated the activities of five broad-spectrum antimicrobial peptides (AMPs) against several important swine-origin pathogenic viruses by TCID 50 assay. Plaque reduction assay and cell apoptosis assay were also used to test the activity of the peptides. Protection effect of piscidin against pseudorabies virus (PRV) was also examined in mouse model. Results: Piscidin (piscidin 1), caerin (caerin 1.1) and maculatin (maculatin 1.1) could inhibit PRV by direct interaction with the virus particles in a dose-dependent manner and they could also protect the cells from PRV-induced apoptosis. Among the peptides tested, piscidin showed the strongest activity against PRV. Moreover, in vivo assay showed that piscidin can reduce the mortality of mice infected with PRV. Conclusion: In vitro and in vivo experiments indicate that piscidin has antiviral activity against PRV.
Output: Antiviral activity of Piscidin 1 against pseudorabies virus both in vitro and in vivo
The rebirth of modern analytical ultracentrifugation (AUC) began in 1990s. Since then many advanced AUC detectors have been developed that provide a vast range of versatile choices when characterizing the physical and chemical features of macromolecules. In addition, there have been remarkable advances in software that allow the analysis of AUC data using more sophisticated models, including quaternary structures, conformational changes, and biomolecular interactions. Here we report the application of AUC to protein size-and-shape distribution analysis and structure-and-function analysis in the presence of ligands or lipids. Using band-sedimentation velocity, quaternary structural changes and an enzyme's catalytic activity can be observed simultaneously. This provides direct insights into the correlation between quaternary structure and catalytic activity of the enzyme. On the other hand, also in this study, we have applied size-and-shape distribution analysis to a lipid-binding protein in either an aqueous or lipid environment. The sedimentation velocity data for the protein with or without lipid were evaluated using the c(s,f r ) two-dimensional distribution model, which provides a precise and quantitative means of analyzing the protein's conformational changes.
Output: Applications of analytical ultracentrifugation to protein size-and-shape distribution and structure-and-function analyses