niryuu/sni-each-converted huggingface dataset:
Upper respiratory tract infections (URIs) are a major cause of morbidity among vocal arts professionals, both from their acute impairment of the vocal mechanism and their predisposing influence for the development of serious vocal sequelae. In this review, we present some of the salient features of currently available treatments effective against influenza, the virus family responsible for the most serious form of URI. At present, these include an inactivated vaccine and four antiviral drugs, each approved in the United States and many other countries for the prevention and treatment of influenza. A live attenuated vaccine is also available, and other vaccines and antiviral drugs are under development. This review details the current options available for treating both influenza and noninfluenza related URIs in the professional voice user.
Output: Influenza and the Vocal Performer: Update on Prevention and Treatment
We have examined the requirement for ribonucleotides and ribonucleotide triphosphate hydrolysis during early events in the membrane integration of two membrane proteins: the G protein of vesicular stomatitis virus and the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus. Both proteins contain a single transmembrane-spanning segment but are integrated in the membrane with opposite orientations. The G protein has an amino-terminal signal sequence and a stop-transfer sequence located near the carboxy terminus. The HN glycoprotein has a single sequence near the amino terminus that functions as both a signal-sequence and a transmembrane-spanning segment. Membrane insertion was explored using a cell-free system directed by transcribed mRNAs encoding amino-terminal segments of the two proteins. Ribosome-bound nascent polypeptides were assembled, ribonucleotides were removed by gel filtration
Output: Integration of Membrane Proteins into the Endoplasmic Reticulum Requires GTP
cells) were constructed. Then MDBK, GFP-LC3-MDBK and shBCN1-MDBK cells were infected with CP or NCP BVDV strains. The LC3-II turnover rate was estimated by western blot, autophagosomes were visualized by confocal microscopy, and ultrastructural analysis was performed using electron microscopy. Autophagy flux was observed using chloroquine as an inhibitor of the autophagic process. The influence of autophagy on BVDV replication and release was investigated using virus titration, and its effect on cell viability was also studied. The effect of BVDVinduced autophagy on the survival of BVDV-infected host cell, cell apoptosis, and interferon (IFN) signalling was studied by flow cytometric analysis and quantitative RT-(q)PCR using shBCN1-MDBK cells. we found that infection with either CP or NCP BVDV strains induced steady-state autophagy in MDBK cells, as evident by the increased number of double-or single-membrane vesicles, the accumulation of GFP-microtubule-associated protein 1 light chain 3 (LC3) dots, and the conversion of LC3-I (cytosolic) to LC3-II (membrane-bound) forms. The complete autophagic process was verified by monitoring the LC3-II turnover ratio, lysosomal delivery, and proteolysis. In addition, we found that CP and NCP BVDV growth was inhibited in MDBK cells treated with high levels of an autophagy inducer or inhibitor, or in autophagy deficient-MDBK cells. Furthermore, our studies also suggested that CP and NCP BVDV infection in autophagy-knockdown MDBK cells increased apoptotic cell death and enhanced the expression of the mRNAs for IFN-α, Mx1, IFN-β, and OAS-1 as compared with control MDBK cells. Our study provides strong evidence that BVDV infection induces autophagy, which facilitates BVDV replication in MDBK cells and impairs the innate immune response. These findings might help to illustrate the pathogenesis of persistent infection caused by BVDV. Abstract Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle that plays a complex role in disease. There are two biotypes of BVDV: non-cytopathic (NCP) and cytopathic (CP). One strategy that has been used to treat or prevent virus-associated diseases is the modulation of autophagy, which is used by the innate immune system to defend against viral infection; however, at present, the interplay between autophagy and BVDV remains unclear. Madin-Darby bovine kidney cells stably expressing microtubule-associated protein 1 light chain 3B (LC3B) with green fluorescent protein (GFP) (GFP-LC3-MDBK cells) and autophagy-deficient MDBKs (shBCN1-MDBK Yulong Zhou and Yachao Ren have contributed equally to this work.
Output: Autophagy induced by bovine viral diarrhea virus infection counteracts apoptosis and innate immune activation
on behalf of the members of the MERS-CoV outbreak investigation team of The Netherlands Abstract Background: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. Methods: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. Results: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. Conclusions: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.
Output: Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014
Protein ubiquitylation is an important regulator of protein function, localization and half-life. It plays a key role in most cellular processes including immune signaling. Deregulation of this process is a major causative factor for many diseases. A major advancement in the identification and characterization of the enzymes that remove ubiquitin, deubiquitylases (DUBs) was made by the development of activity-based probes (ABPs). Recent advances in chemical protein synthesis and ligation methodology has yielded novel reagents for use in ubiquitylation research. We describe recent advances and discuss future directions in reagent development for studying DUBs.
Output: Catching a DUB in the act: novel ubiquitin-based active site directed probes
1990). Fundam. Appl. Toxicol. 15, 12 l-l 3 1. Although ozone-induced epithelial injury in vivo has been morphologically characterized, effects of gaseous oxidants on respiratory epithelium in organ culture, where tissue organization is maintained but systemic influences are eliminated, have not been thoroughly investigated. In this study, we exposed tracheal organ cultures from rats to 95% oxygen and 1 ppm ozone. alone and in combination, to determine (1) whether epithelial responses to ozone similar to those observed in vivo occur in airways separated from systemic physiologic, secretory, and inflammatory reactions; (2) whether concentrations of oxygen sufficient to potentially cause oxidant injury result in morphologic epithelial alterations similar to those that occur in ozone toxicity: and (3) if the combined oxidant insult of oxygen and ozone results in more severe damage to the tracheal epithelium than occurs with ozone in air. Tracheal organ cultures were exposed to filtered air and 5% carbon dioxide; filtered air, 5% carbon dioxide, and 1 ppm ozone; 95% oxygen and 5% carbon dioxide: or 95% oxygen, 5% carbon dioxide, and 1 ppm ozone for 96 hr. Light-and quantitative electron-microscopic evaluation showed that epithelia exposed to 1 ppm ozone in air exhibited loss of ciliated cells and ciliated cell damage. The epithelia exposed to 95% oxygen and 5% carbon dioxide were pseudostratified. columnar, ciliated, and hyperplastic. Epithelia exposed to 95% oxygen plus 1 ppm ozone were stratified and nonciliated or very sparsely ciliated. The predominant cell types in epithelia exposed to oxygen plus ozone were serous cells and metaplastic cells. and focal aggregates of adherent necrotic cells were present. We conclude that there was a synergism between oxygen and ozone exposure leading to enhanced epithelial injury and metaplasia. 0 1990 Society ofToxicology.
Output: Response of Rat Tracheal Epithelium to Ozone and Oxygen Exposure in Vitro
The sudden emergence of severe acute respiratory syndrome (SARS) has boosted research on innate immune responses to coronaviruses. It is now well established that the causative agent, a newly identified coronavirus termed SARS-CoV, employs multiple passive and active mechanisms to avoid induction of the antiviral type I interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are strongly upregulated. The imbalance in the IFN response is thought to contribute to the establishment of viremia early in infection, whereas the production of chemokines by infected organs may be responsible for (i) massive immune cell infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of adaptive immunity. Here, we will review the most recent findings on the interaction of SARS-CoV and related Coronaviridae members with the type I interferon and cytokine responses and discuss implications for pathogenesis and therapy. #
Output: Interferon and cytokine responses to SARS-coronavirus infection
Work-related mental health impairment is recognized as a real problem in the context of helping responders, including health professionals, due to adverse health outcomes after a severe disaster. The Great East-Japan Earthquake, which occurred on 11 March 2011, was an unprecedented complex disaster that caused a nuclear accident at the Fukushima Daiichi Nuclear Power Plant (NPP). In addition to disaster stress and daily work, medical and health-care professionals, particularly nurses, provided counseling services to residents concerned about radiation health risks or mental health issues. This review focuses on the psychological aspects of the complex nuclear disaster, which was a combined artificial nuclear accident and natural disaster, and we investigated the psychological effects on hospital nurses associated with their experiences during the disaster. We looked at several investigations into the mental health of nurses after a nuclear disaster and in other situations. It was shown that mental health of nurses is impacted, not only after nuclear disasters but also in other circumstances. Furthermore, we noted the effects of extended periods of a heavy workload and daily life. Regarding anxiety about radiation exposure, nurses who had more knowledge of radiation tended to have better mental health, suggesting that education about the health risks of radiation exposure is important for health-care professionals. In summary, it is essential that nurses are provided with education about radiation exposure and its associated health risks, and also that there is a comprehensive approach to mental health care for nurses during the chronic phase of a disaster.
Output: Mental health of nurses after the Fukushima complex disaster: a narrative review
Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections. and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.
Output: Heparan Sulfate-Dependent Enhancement of Henipavirus Infection
Background: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. Methods: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8uC and 37.5uC) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). Findings: Using front of face ITIS for prediction of tympanic temperature $37.8uC, the area under the ROC curve was 0.86 (95%CI 0.75-0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56-0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature $37.8uC at screening (95%CI 0% to 12%); three had no influenza symptoms. Conclusion: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.
Output: Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study
The acute respiratory distress syndrome (ARDS) is a lethal inflammatory disorder of the lung. Its incidence is estimated at 75 cases per 100,000 population and appears to be increasing [1] . Even with optimal treatment, mortality is about 30% [1-3]. As such, ARDS represents a major public health problem. The effects of two recent crises created by unusual viral infections of the respiratory tract -the severe acute respiratory syndrome (SARS) epidemic caused by the novel SARS coronavirus [4, 5] and the bird flu [6] highlight the importance of research into ARDS. Both viruses cause an ARDS-like picture. Because lung repair and regeneration contribute substantially to the pathophysiology of ARDS, understanding these processes is essential [7] . This chapter focuses on specific cell populations and markers involved in cell division and regeneration. In addition, a brief review of two pathways intimately associated with cell division is provided because of their potential for pharmacologic manipulation.
Output: Cell Regeneration in Lung Injury
Background: Middle East respiratory syndrome coronavirus (MERS-CoV) caused multiple outbreaks. Such outbreaks increase economic and infection control burdens. We studied the infection control influence of MERS-CoV using a hospital-based analysis. Methods: Our hospital had 17 positive and 82 negative cases of MERS-CoV between April 1, 2013, and June 3, 2013. The study evaluated the impact of these cases on the use of gloves, surgical masks, N95 respirators, alcohol-based hand sanitizer, and soap, as well as hand hygiene compliance rates. Results: During the study, the use of personal protective equipment during MERS-CoV compared with the period before MERS-CoV increased dramatically from 2,947.4 to 10,283.9 per 1,000 patient-days (P < .0000001) for surgical masks and from 22 to 232 per 1,000 patient-days (P < .0000001) for N95 masks. The use of alcohol-based hand sanitizer and soap showed a significant increase in utilized amount (P < .0000001). Hand hygiene compliance rates increased from 73% just before the occurrence of the first MERS case to 88% during MERS cases (P = .0001). The monthly added cost was $16,400 for included infection control items. Conclusions: There was a significant increase in the utilization of surgical masks, respirators, soap and alcohol-based hand sanitizers. Such an increase is a challenge and adds cost to the healthcare system.
Output: Infection control influence of Middle East respiratory syndrome coronavirus: A hospital-based analysis
Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18-64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 g, 15 g, or 45 g hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 g VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 g and 45 g) compared to the placebo and 5 g VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82-92% of all subjects and in 64-85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.
Output: Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico
Cruzain is a member of the papain/cathepsin-L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. We report an auto-induction methodology that provides soluble-cruzain at high yields (> 30 mg per liter in minimal media). These increased yields provide sufficient quantities of active enzyme for use in NMR-based ligand mapping. Using CD and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective 15 N-Cys, 15 N-His, and 13 C-Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verifies that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely covalent, non-covalent, and non-interacting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions in order to facilitate lead compound identification and subsequent structural studies.
Output: Mapping Inhibitor Binding Modes on an Active Cysteine Protease via NMR Spectroscopy
G-quadruplexes are non-canonical nucleic acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of putative G-quadruplexes in the genome of all known viruses that can infect humans. We show that the presence, distribution, and location of G-quadruplexes are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the G-quadruplex classification. For each virus we provide: i) the list of all G-quadruplexes formed by GG-, GGG-and GGGG-islands present in the genome (positive and negative strands), ii) their position in the viral genome along with the known function of that region, iii) the degree of conservation among strains of each G-quadruplex in its genome context, iv) the statistical significance of G-quadruplex formation. This information is accessible from a database
Output: G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide Running title: Presence and conservation of G4s in human viruses
Mutation rates can evolve through genetic drift, indirect selection due to genetic hitchhiking, or direct selection on the physicochemical cost of high fidelity. However, for many systems, it has been difficult to disentangle the relative impact of these forces empirically. In RNA viruses, an observed correlation between mutation rate and virulence has led many to argue that their extremely high mutation rates are advantageous because they may allow for increased adaptability. This argument has profound implications because it suggests that pathogenesis in many viral infections depends on rare or de novo mutations. Here, we present data for an alternative model whereby RNA viruses evolve high mutation rates as a byproduct of selection for increased replicative speed. We find that a poliovirus antimutator, 3D G64S , has a significant replication defect and that wild-type (WT) and 3D G64S populations have similar adaptability in 2 distinct cellular environments. Experimental evolution of 3D G64S under selection for replicative speed led to reversion and compensation of the fidelity phenotype. Mice infected with 3D G64S exhibited delayed morbidity at doses well above the lethal level, consistent with attenuation by slower growth as opposed to reduced mutational supply. Furthermore, compensation of the 3D G64S growth defect restored virulence, while compensation of the fidelity phenotype did not. Our data are consistent with the kinetic proofreading model for biosynthetic reactions and suggest that speed is more important than accuracy. In contrast with what has been suggested for many RNA viruses, we find that within-host spread is associated with viral replicative speed and not standing genetic diversity. Why organisms have different mutation rates is a longstanding question in evolutionary biology. The polymerases of RNA viruses generally lack proofreading activity and exhibit extremely high mutation rates. Because most mutations are deleterious and mutation PLOS Biology | https://doi.org/10.1371/journal.pbio.Citation: Fitzsimmons WJ, Woods RJ, McCrone JT, Woodman A, Arnold JJ, Yennawar M, et al. (2018) A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus. PLoS Biol 16(6): e2006459. https://doi.The funder had no role in study design, data collection and analysis, decision to publish, or preparation of rates are typically tuned by natural selection, we asked why RNA viruses haven't evolved a polymerase with a lower mutation rate. We used experimental evolution and a murine infection model to show that RNA virus mutation rates may actually be too high and are not necessarily adaptive. Rather, our data indicate that viral mutation rates have evolved to be higher as a result of selection for viruses with faster replication kinetics. We suggest that viruses have high mutation rates, not because they facilitate adaptation but because it is hard to be both fast and accurate and these viruses have prioritized speed over fidelity. Speed-fidelity trade-off PLOS Biology | https://doi.org/10.1371/journal.pbio.
Output: A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus
Throughout evolutionary history, humans have been exposed to a wide variety of diseases, some of which have serious and even lethal consequences. Memorizing medicinal plants for the treatment of serious diseases likely maximized the chances of survival and reproduction and was instrumental in the evolutionary success of our species. In the present study, we used the idea of adaptive memory to understand whether human memory evolved to recall information about medicinal plants for the treatment of serious diseases. We considered plant-disease pairs of words as units of information available in a medical system based on the use of medicinal plants. The pairs included in the categories of chronic infectious diseases and transmissible infectious diseases were considered to be of higher adaptive value, whereas those included in the category of common conditions were considered to be of lower adaptive value. Pairs grouped into the category of emerging and reemerging diseases were employed to investigate conformity bias; pairs belonging to the category esthetic uses were considered to be of little adaptive relevance and utilized as an experimental control. Our results revealed that plant-disease pairs associated with the category of common conditions, considered by us to be of lower severity and less adaptive relevance for humans, were better remembered and retained in the participants' memory. We believe that prior experience with common conditions and the frequency of these conditions in the population may have intensified the ability to remember the plant-disease pairs associated with this group of diseases. OPEN ACCESS Citation: Henriques da Silva R, Ferreira Júnior WS, Muniz de Medeiros P, Albuquerque UP (2019) Adaptive memory and evolution of the human naturalistic mind: Insights from the use of medicinal plants. PLoS ONE 14(3): e0214300.
Output: Adaptive memory and evolution of the human naturalistic mind: Insights from the use of medicinal plants
Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication. Suppressing the level and transcriptional activity of cccDNA might have anti-HBV effect. Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood. In this study we showed that CREBregulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues. Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription. CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription. Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised. In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription. Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.
Output: Requirement of CRTC1 coactivator for hepatitis B virus transcription
HIV-infected patients may acquire new viral co-infections; they may also experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIVinfected patients may be predisposed to these viral infections due to immunodeficiency or to risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.
Output: Viruses & kidney disease: beyond HIV
Invasive wildlife species have the potential to act as additional host and vector species for infectious diseases. The raccoon dog (Nyctereutes procyonides), a carnivore species that has its origin in Asia, was taken as an example to demonstrate biological and ecological prerequisites which enables an invasive species to occupy a new habitat permanently. Studies conducted during the last 20 years identified a total of 35 species of endoparasites, five ectoparasites, six bacterial or protozoan species, and five viruses found in the subspecies Nyctereutes procyonoides ussuriensis in its original and newly occupied habitat or in Nyctereutes procyonoides koreensis in its original habitat, respectively. With reference to raccoon dogs impact as vector species and the relevance for human and animal health, we selected Trichinella spp., Echinococcus multilocularis, Francisella tularensis, rabies virus, and canine distemper virus for detailed description. Results of studies from Finland and Germany furthermore showed that biological characteristics of the raccoon dog make this carnivore an ideal host and vector for a variety of pathogens. This may result in a growing importance of this invasive species concerning the epidemiology of some transmissible diseases in Europe, including the hazard that the existence of autochthonous wildlife, particularly small populations, is endangered. Potential adverse effects on human and animal health in the livestock sector must also be taken into account. Especially with regard to its potential as a reservoir for zoonotic diseases, the raccoon dog should receive more attention in disease prevention and eradication strategies.
Output: The biological potential of the raccoon dog (Nyctereutes procyonoides, Gray 1834) as an invasive species in Europe-new risks for disease spread?
The cleavage and fusion properties of recombinant murine hepatitis viruses (MHV) were examined to assess the role of the cleavage signal in determining the extent of S protein cleavage, and the correlation between cleavage and induction of cell-to-cell fusion. Targeted recombination was used to introduce amino acid substitutions into the cleavage signal of the fusion glycoprotein (spike or S protein) of MHV strain A59. The recombinants were then used to address the question of the importance of S protein cleavage and viralmediated cell-to-cell fusion on pathogenicity. Our data indicate that cleavage of spike is not solely determined by the amino acid sequence at the cleavage site, but may also depend on sequences removed from the cleavage site. In addition, ef cient cell-to-cell fusion is not necessary for virulence. Journal of NeuroVirology (2002) 8, 400-410.
Output: The virulence of mouse hepatitis virus strain A59 is not dependent on ef cient spike protein cleavage and cell-to-cell fusion
Despite widespread use of communicable disease surveillance data to inform public health intervention and control measures, the reporting completeness of the notifiable disease surveillance system remains incompletely assessed. Therefore, we conducted a comprehensive study of reporting completeness with an analysis of 53 diseases reported by 8 health care systems across North Carolina, USA, during 1995USA, during -1997USA, during and 2000USA, during -2006. All patients who were assigned an International Classifi cation of Diseases, 9th Revision, Clinical Modifi cation, diagnosis code for a state-required reportable communicable disease were matched to surveillance records. We used logistic regression techniques to estimate reporting completeness by disease, year, and health care system. The completeness of reporting varied among the health care systems from 2% to 30% and improved over time. Disease-specifi c reporting completeness proportions ranged from 0% to 82%, but were generally low even for diseases with great public health importance and opportunity for interventions.
Output: Author affi liations: University of North Carolina Health Care Sys-tem
The viral ribonucleoprotein complex of human immunodeficiency virus-1 (HIV-1) associates with the viral Envelope (Env) to form infectious virions. While Env and Gag are known to migrate to lipid microdomains, their stoichiometry and specificity of interaction is not known. Here, we analyze the association of different viral glycoproteins, HIV Env and Ebola GP, with HIV-1 Gag protein co-expressed in the same cell. Though these two viral spikes were both expressed, each associated independently with Gag and gave rise to two distinct virion populations, each with a spike of a single type. Confocal imaging demonstrated that HIV Env 89.6 and Ebola GP localized to distinct lipid raft microdomains within the same cell, where each associated with distinct Gag particles. Similar Env localization was observed in HIV-infected T cells, where ~14 percent of Env was associated with Gag during productive infection. Together, these data suggest that a single Gag complex associates "quantally" with an individual lipid raft microdomain to assemble functional virions during infection.
Output: Quantal formation of lentiviruses in cells: segregation of viral glycoproteins to lipid rafts that associate individually with HIV-1 Capsids
In this paper, we present a new microfluidic immunoassay platform, which is based on the synergistic combination of the yeast surface display (YSD) technique and the microfluidic technology. Utilizing the YSD technique, antigens specific to the target antibody are displayed on the surface of engineered yeast cells with intracellular fluorescent proteins. The displayed antigens are then used for the detection of the target antibody, with the yeast cells as fluorescent labels. Multiplex immunoassay can be readily realized by using yeast cells expressing different intracellular fluorescent proteins to display different antigens. The implementation of this YSD-based immunoassay on the microfluidic platform eliminates the need for the bulky, complex and expensive flow cytometer. To improve the detection sensitivity and to eliminate the need for pumping, a functionalized micro pillar array (MPA) is incorporated in the microfluidic chip, resulting in a detection limit of 5 ng/mL (or 1 ng in terms of amount) and enhanced compatibility with practical applications such as clinical biopsy. This new platform has a high potential to be integrated into microfluidic detection systems to enable portable diagnostics in the future.
Output: Yeast surface display-based microfluidic immunoassay
Purpose: The study aimed to examine query strategies that would provide an exhaustive search method to retrieve the most referenced articles within specific categories of critical care. Material and Methods: A comprehensive list of the most cited critical care medicine articles was generated by searching the Science Citation Index Expanded data set using general critical care terms keywords such as "critical care," critical care journal titles, and keywords for subsubjects of critical care. Results: The final database included 1187 articles published between 1905 and 2006. The most cited article was referenced 4909 times. The most productive search term was intensive care. However, this term only retrieved 25% of the top 100 articles. Furthermore, 662 of the top 1000 articles could not be found using any of the basic critical care search terms. Sepsis, acute lung injury, and mechanical ventilation were the most common areas of focus for the articles retrieved. Conclusion: Retrieving frequently cited, influential articles in critical care requires using multiple search terms and manuscript sources. Periodic compilations of most cited articles may be useful for critical care practitioners and researches to keep abreast of important information.
Output: A View of the Literature The most influential articles in critical care medicine ☆
Chronic obstructive pulmonary disease (COPD) is a disease with high prevalence and substantial associated economical burden. A significant determinant of quality of life, long-term survival, and health care costs is an acute exacerbation of COPD. Acute exacerbations are provoked by respiratory viruses, altered airway microbiome, and environmental factors. The current treatment options are limited. In order to develop specific therapeutic measures, it is important to understand how acute exacerbations evolve. This review focuses on pathophysiology of stable and exacerbated COPD.
Output: Exacerbation of Chronic Obstructive Pulmonary Disease
INcnak! G. A. and AL-YAMAN F. 1988. A comparative assessment of four serological methods used in the detection and measurement of anti-parasite antibodies in the serum of the amphibian, Bufo viridis. International Journal for Parasitology 18: 371-377. Antibodies against Cn'thidia fasciculata choanomastigotes were detected in green toad (Bufo viridis) sera by direct agglutination, indirect haemagglutination (IHA), complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA). Correlation coefficients (r) were calculated for comparisons between each of the techniques and regression formulae derived in order to convert antibody levels as determined by one immunological method to that of another. The highest mean titre obtained by ELISA was approximately 1.5-3.5 times greater than those obtained by the other techniques whilst CFT gave the lowest values. IHA and ELISA titres were affected by different preparations of the crithidial antigen extracts. Highly significant r values were determined for control sera when IHA was compared to ELISA (r> 0.79), and to both CFT and ELISA with immune animals (r> 0.96). ELISA would seem most applicable for screening other lower vertebrates for anti-parasite antibodies especially in areas of human disease prevalence.
Output: A COMPARATIVE ASSESSMENT OF FOUR SEROLOGICAL METHODS USED IN THE DETECTION AND MEASUREMENT OF ANTI-PARASITE ANTIBODIES IN THE SERUM OF THE AMPHIBIAN, BUFO K!XIDIs
Administration of recombinant feline interferon-v (rFeIFN) has been proposed for the prophylaxis of canine and feline parvovirosis. In the present study, the influence of the administration of rFeIFN on blood markers of inflammation (a-globulins, a 1acid glycoprotein) and immune system activation (g-globulins, IgG, IgM, specific anti-feline parvovirus IgG or IgM) was evaluated in a cattery developing an outbreak of feline panleukopenia due to feline parvovirus (FPV) infection few days after initial administration of rFeIFN. Kittens (n = 23) were injected with rFeIFN (1 MU/kg subcutaneoulsy, once a day for 3 days) and their blood parameters were compared with those of 17 untreated cats. Cats that survived the outbreak were vaccinated and re-sampled 1 month after the last rFeIFN administration. Time of emergence of clinical signs and survival rate were not significantly different between the two groups. Controls and treated cats surviving the infection had high levels of g-globulins, total-and anti-FPV specific IgGs, likely due to passive transfer of maternal immunity. Compared to controls, treated kittens had lower levels of a 1 -globulins and higher mean values of g-globulins and immunoglobulins. Data from samples collected after vaccination revealed a higher level of gglobulins, total-and anti-FPV specific IgGs in treated kittens, compared with controls, suggesting that rFeIFN stimulates antibody production. Based on this results, rFeIFN should be administered to the queen, to increase passive maternal immunity, or to kittens before introduction in a potentially contaminated environment. # * P < 0.05 vs. CI. y P < 0.05 vs. CII and vs. TI.
Output: Evaluation of inflammation and immunity in cats with spontaneous parvovirus infection: Consequences of recombinant feline interferon-v administration
To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp. associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses.
Output: New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences
Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structureeactivity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.
Output: Therapeutic potential of coumarins as antiviral agents
because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20's antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. The envelope glycoprotein (Env) of the human immunodeficiency virus type 1 (HIV-1) includes the gp120 surface subunit and the gp41 transmembrane subunit. As a class I transmembrane protein, gp41 plays a significant role in the membrane fusion and virus entry of HIV-1 1,2 . After the binding of the gp120 to the cellular receptors, gp41 undergoes conformation changes after fusion peptide (FP) inserts into the
Output: Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy OPEN
The use of small animal models for the study of infectious disease is critical for understanding disease progression and for developing prophylactic and therapeutic treatment options. For many diseases, Syrian golden hamsters have emerged as an ideal animal model due to their low cost, small size, ease of handling, and ability to accurately reflect disease progression in humans. Despite the increasing use and popularity of hamsters, there remains a lack of available reagents for studying hamster immune responses. Without suitable reagents for assessing immune responses, researchers are left to examine clinical signs and disease pathology. This becomes an issue for the development of vaccine and treatment options where characterizing the type of immune response generated is critical for understanding protection from disease. Despite the relative lack of reagents for use in hamsters, significant advances have been made recently with several hamster specific immunologic methods being developed. Here we discuss the progress of this development, with focus on classical methods used as well as more recent molecular methods. We outline what methods are currently available for use in hamsters and what is readily used as well as what limitations still exist and future perspectives of reagent and assay development for hamsters. This will provide valuable information to researchers who are deciding whether to use hamsters as an animal model. Syrian hamster • Golden hamster • Syrian golden hamster • Immunological tools • Molecular methods • Mesocricetus auratus • Animal models
Output: Syrian Hamsters as a Small Animal Model for Emerging Infectious Diseases: Advances in Immunologic Methods