niryuu/sni-each-converted huggingface dataset:
Background: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. Methods: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/-were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. Results: 3xTgQ-/-mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/-on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. Conclusions: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.
Output: Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease
Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. The related feline enteric coronavirus (FECV) causes mild enteritis. Why these feline coronaviruses manifest so differently in vivo is not known. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. The infection kinetics in monocytes were host dependent. Monocytes from 1 cat were resistant to both FIPV-and FECV-infection. Monocytes from the other 2 cats could initially be infected by both FIPV and FECV but FIPV infection was sustained in monocytes of only one cat. FECV-infection was never sustained and viral production was up to 100 times lower than in FIPVinfected monocytes. In CrFK cells, FIPV and FECV infection kinetics did not differ. In monocytes of a larger cat population (n = 19) the 3 infection patterns were also found. Considering all 22 investigated cats, 3/22 were not susceptible for FIPV and FECV. The rest could be infected with FECV and FIPV but 10/22 cats had monocytes that only sustained FIPV infection and 9/22 sustained neither FIPV nor FECV infection. * Both authors contributed equally.
Output: Replication of feline coronaviruses in peripheral blood monocytes
This study is designed to conceptually propose and empirically examine a theoretical model for restaurant diners' self-protective behavior in response to an epidemic crisis. Based on Weinstein's five-stage PAPM, a prospective model and a classification scheme for five corresponding types of self-protective behavior adopters are proposed in this study. By using ten-year longitudinal survey data provided by a timely research sample which was obtained from a multi-store restaurant's diner club members immediately after the peak period of the SARS outbreak in Taiwan, both theoretical and managerial applicability of the proposed stage-based model are empirically verified in this study. The results show that the type of self-protective behavior respondents adopted is significantly associated with their marital status and risk attitude toward the epidemic. Besides, respondents significantly advance their type of self-protective behavior adoption along successive epidemics from the SARS to avian influenza A(H7N9) in decade.
Output: Restaurant diners' self-protective behavior in response to an epidemic crisis
Influenza viruses are enveloped, negative stranded, segmented RNA viruses belonging to Orthomyxoviridae family. Each virion consists of three major subviral components, namely (i) a viral envelope decorated with three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and M2, (ii) an intermediate layer of matrix protein (M1), and (iii) an innermost helical viral ribonucleocapsid [vRNP] core formed by nucleoprotein (NP) and negative strand viral RNA (vRNA). Since complete virus particles are not found inside the cell, the processes of assembly, morphogenesis, budding and release of progeny virus particles at the plasma membrane of the infected cells are critically important for the production of infectious virions and pathogenesis of influenza viruses as well. Morphogenesis and budding require that all virus components must be brought to the budding site which is the apical plasma membrane in polarized epithelial cells whether in vitro cultured cells or in vivo infected animals. HA and NA forming the outer spikes on the viral envelope possess apical sorting signals and use exocytic pathways and lipid rafts for cell surface transport and apical sorting. NP also has apical determinant(s) and is probably transported to the apical budding site similarly via lipid rafts and/or through cortical actin microfilaments. M1 binds the NP and the exposed RNAs of vRNPs, as well as to the cytoplasmic tails (CT) and transmembrane (TM) domains of HA, NA and M2, and is likely brought to the budding site on the piggy-back of vRNP and transmembrane proteins. Budding processes involve bud initiation, bud growth and bud release. Presence of lipid rafts and assembly of viral components at the budding site can cause asymmetry of lipid bilayers and outward membrane bending leading to bud initiation and bud growth. Bud release requires fusion of the apposing viral and cellular membranes and scission of the virus buds from the infected cellular membrane. The processes involved in bud initiation, bud growth and bud scission/release require involvement both viral and host components and can affect bud closing and virus release in both positive and negative ways. Among the viral components, M1, M2 and NA play important roles in bud release and M1, M2 and NA mutations all affect the morphology of buds and released viruses. Disassembly of host cortical actin microfilaments at the pinching-off site appears to facilitate bud fission and release. Bud scission is energy dependent and only a small fraction of virus buds present on the cell surface is released. Discontinuity of M1 layer underneath the lipid bilayer, absence of outer membrane spikes, absence of lipid rafts in the lipid bilayer, as well as possible presence of M2 and disassembly of cortical actin microfilaments at the pinching off site appear to facilitate bud fission and bud release. We provide our current understanding of these important processes leading to the production of infectious influenza virus particles.
Output: Influenza virus morphogenesis and budding NIH Public Access NIH-PA Author Manuscript
The spatial and spatio-temporal scan statistics proposed by Kulldorff have been applied to a number of geographical disease cluster detection problems. As the shape of the scanning window used in these methods is circular or elliptic, they cannot find irregularly shaped clusters, say clusters occurring along river valleys or in cases where disease transmission is linked to the road network. In this study, we propose a more flexible geometric structure to be used as a spatial or spatio-temporal scanning window. A particle swarm optimization (PSO) is used to optimize the scanning window to determine disease clusters. We evaluated the proposed method over a number of spatial and spatio-temporal datasets (Breast cancer mortality in Northeastern US 1988-1992 and different types of cancer in New Mexico 1982 -2007 . Experimental results demonstrate that the introduced approach surpasses the results produced by the circular and elliptic scan statistics in terms of efficiency, especially when dealing with irregularly shaped clusters.
Output: Regular paper A new PSO-optimized geometry of spatial and spatio-temporal scan statistics for disease outbreak detection
Background: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. Results: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.
Output: Open Access RESEARCH Proteomic analysis of purified coronavirus infectious bronchitis virus particles
Hundreds of different species colonize multicellular organisms making them "metaorganisms". A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole-may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly crossspecies consequences.
Output: Structural host-microbiota interaction networks
To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection.
Output: Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up
We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 39 end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 908 kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold. Citation: Robertson MP, Igel H, Baertsch R, Haussler D, Ares M, et al. (2004) The structure of a rigorously conserved RNA element within the SARS virus genome. PLoS Biol 3(1): e5. PLoS Biology | www.plosbiology.org January 2005 | Volume 3 | Issue 1 | e5 0086 Open access, freely available online PL o S BIOLOGY PLoS Biology | www.plosbiology.org January 2005 | Volume 3 | Issue 1 | e5 0087 Crystal Structure of SARS s2m RNA PLoS Biology | www.plosbiology.org
Output: The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome
The bacterial bipartite transferrin receptor is an iron acquisition system that is required for 12 survival by several key human and animal pathogens. It consists of the TonB-dependent 13 transporter Transferrin binding protein A (TbpA) and the surface lipoprotein Transferrin binding 14 protein B (TbpB). Curiously, the Tbps are only found in host specific pathogens, and are 15 themselves host specific, meaning that they will bind to the transferrin of their host species, but 16 not to those of other animal species. While this phenomenon has long been established, neither 17 the steps in the evolutionary process that led to this exquisite adaptation for the host, nor the 18 steps that could alter it, are known. We sought to gain insight into these processes by studying 19 Tbp specificity in Histophilus somni, a major pathogen of cattle. A past study showed that whole 20 cells of H. somni specifically bind bovine transferrin, but not transferrin from sheep and goats, 21 two bovids whose transferrins share 93% amino acid sequence identity with bovine transferrin. 22 To our surprise, we found that H. somni can use sheep and goat transferrins as iron sources for 23 growth, and that HsTbpB, but not HsTbpA, has detectable affinity for sheep and goat 24 transferrins. Furthermore, a third transferrin binding protein, HsTbpA2, also showed affinity for 25 sheep and goat transferrins. Our results show that H. somni TbpB and TbpA2 act to broaden the 26 host transferrin recognition range of H. somni. 27
Output: Transferrin binding protein B and Transferrin binding protein A 2 expand the transferrin 1 recognition range of Histophilus somni 2 3 Running title: TbpB and TbpA2 broaden specificity of
This study numerically investigated the thermal effect of human body on the time-dependent dispersion of cough droplets with evaporation process. The thermal flow of human body was imitated using a 3D thermal manikin with real body features, while a recent developed multi-component Eulerian-Lagrangian approach was used to address the effects of inhomogeneous temperature and humidity fields on droplet evaporation. By comparing the results yielded without and with the human body heat, the outcomes demonstrated strong impact of human body heat on the droplets mass fraction and local air velocity distributions. Inspirable droplets could potentially drop into respirable droplets by evaporation, although the evaporation rate was not significantly affected by body heat. The thermal effect of human body revealed its vital impacts on the time-dependent droplets dispersion. Due to the buoyancy driven thermal flow, both the vertical velocity and displacement of small droplets (≤20 μm) were completely reversed from descending to ascending, while the deposition time of large droplets (≥50 μm) were significantly delayed. With the reduced droplet size by evaporation and droplets lifted into breathing zone by human thermal effect, the inhalability and infection risks of cough droplets would be much higher in real occupied indoor spaces.
Output: Thermal effect of human body on cough droplets evaporation and dispersion in an enclosed space
Numerous preclinical studies have demonstrated the efficacy of viral gene delivery vectors, and recent clinical trials have shown promising results. However, the tight control of transgene expression is likely to be required for therapeutic applications and in some instances, for safety reasons. For this purpose, several ligand-dependent transcription regulatory systems have been developed. Among these, the tetracyclineregulatable system is by far the most frequently used and the most advanced towards gene therapy trials. This review will focus on this system and will describe the most recent progress in the regulation of transgene expression in various organs, including the muscle, the retina and the brain. Since the development of an immune response to the transactivator was observed following gene transfer in the muscle of nonhuman primate, focus will be therefore, given on the immune response to transgene products of the tetracycline inducible promoter.
Output: In vivo gene regulation using tetracycline-regulatable systems ☆
During dengue outbreaks, acute diagnosis at the patient's point of need followed by appropriate supportive therapy reduces morbidity and mortality. To facilitate needed diagnosis, we developed and optimized a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that detects all 4 serotypes of dengue virus (DENV). We used a quencher to reduce nonspecific amplification. The assay does not require expensive thermocyclers, utilizing a simple water bath to maintain the reaction at 63°C. Results can be visualized using UV fluorescence, handheld readers, or lateral flow immunochromatographic tests. We report a sensitivity of 86.3% (95% confidence interval [CI], 72.7-94.8%) and specificity of 93.0% (95% CI, 83.0-98.1%) using a panel of clinical specimens characterized by DENV quantitative reverse transcription-polymerase chain reaction. This pan-serotype DENV RT-LAMP can be adapted to field-expedient formats where it can provide actionable diagnosis near the patient's point of need.
Output: Development of a pan-serotype reverse transcription loop-mediated isothermal amplification assay for the detection of dengue virus
This study explores the impact of domestic low-cost carriers (LCCs) on regional tourism and aviation industries. In particular, it articulates the changing competitive dynamics between LCCs and full-service carriers (FSCs). The Lotka-Volterra (LV) model, utilising the newly proposed moving-window concept, is used for the assessment of the influence of LCCs on the South Korean and airline industry. Analysis results demonstrate that the competitive dynamics between LCCs and FSCs are not static and have evolved over time. The study proposes an efficient and effective change analysis and enables strategic planning for aviation industries.
Output: Evolving competition between low-cost carriers and full-service carriers: The case of South Korea
1. Predicting infectious disease dynamics is a central challenge in disease ecology. Models 36 that can assess which individuals are most at risk of being exposed to a pathogen not only 37 provide valuable insights into disease transmission and dynamics but can also guide 38 management interventions. Constructing such models for wild animal populations, 39 however, is particularly challenging; often only serological data is available on a subset 40 of individuals and non-linear relationships between variables are common. 41 42 2. Here we take advantage of the latest advances in statistical machine learning to construct 43 pathogen-risk models that automatically incorporate complex non-linear relationships 44 with minimal statistical assumptions from ecological data with missing values. Our 45 approach compares multiple machine learning algorithms in a unified environment to 46 find the model with the best predictive performance and uses game theory to better 47 interpret results. We apply this framework on two major pathogens that infect African 48 lions: canine distemper virus (CDV) and feline parvovirus. 49 50 3. Our modelling approach provided enhanced predictive performance compared to more 51 traditional approaches, as well as new insights into disease risks in a wild population. We 52 were able to efficiently capture and visualise strong non-linear patterns, as well as model 53 complex interactions between variables in shaping exposure risk from CDV and feline 54 parvovirus. For example, we found that lions were more likely to be exposed to CDV at a 55 young age but only in low rainfall years. 56 57 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/569012 doi: bioRxiv preprint 3 4. When combined with our data calibration approach, our framework helped us to answer 58 questions about risk of pathogen exposure which are difficult to address with previous 59 methods. Our framework not only has the potential to aid in predicting disease risk in 60 animal populations, but also can be used to build robust predictive models suitable for 61 other ecological applications such as modelling species distribution or diversity patterns.
Output: How to make more from exposure data? An integrated machine Author Contributions Data Accessibility Statement Running Title Machine learning and pathogen exposure risk
A recombinant baculovirus containing a cDNA which encodes haemagglutininneuraminidase (HN) of Newcastle disease virus (NDV) was constructed. Spodqteru frugiperda cells infected with this recombinant virus produced a large amount of HN glycoprotein similar to the authentic HN in size. The recombinant HN glycoprotein was localized on the surface of the infected cells and conserved its haemadsorption and neuraminidase activities. The antigenic properties of the recombinant HN glycoprotein seemed to be slightly different from the authentic one, as judging by the reactivity with a panel of monoclonal antibodies specific to the antigenic sites responsible for neutralization of viral infectivity. Chickens inoculated with the cells infected with the recombinant virus developed haemagglutination-inhibition and virus neutralization antibodies, and were completely protected from the NDV challenge. Correspondence tot M. Niikura,
Output: Characterization of haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus expressed by a recombinant baculovirus
A major entry route for the gammaretrovirus amphotropic murine leukemia virus (A-MLV) into NIH 3T3 fibroblasts is via caveola-dependent endocytosis. However, during the infection time, few viral particles can be observed intracellularly. Analyzing the dynamics of the A-MLV infection process by using total internal reflection fluorescence microscopy, we show that the majority of viruses are extracellular and bound to the fibronectin matrix. Moreover, the amounts of bound virus and of fibronectin correlated. Using confocal microscopy, nanoparticles targeted to fibronectin by a III1C-fibronectin fragment or anti-fibronectin antibody were detected intracellularly in NIH 3T3 cells; unconjugated nanoparticles neither bound to cells nor were detectable intracellularly. Furthermore, A-MLV colocalized intracellularly with the fibronectin-targeted nanoparticles, suggesting that they were taken up by the same cellular pathway. Both A-MLV entry and fibronectin turnover depend on caveolar endocytosis, and we found that inhibiting viral binding to the extracellular NIH 3T3 fibronectin-matrix dramatically reduced A-MLV infection, indeed, showing an active role of fibronectin in infection. We suggest that binding to the cellular fibronectin matrix provides a new mechanism by which viruses can enter cells.
Output: Matrix Fibronectin Binds Gammaretrovirus and Assists in Entry: New Light on Viral Infections ᰔ † Downloaded from
In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after vaccination, research and development on antiviral agents is being conducted to induce protection until immunological competence is produced. This study tested whether well-known chemicals used as RNA virus treatment agents had inhibitory effects on FMD viruses (FMDVs) and demonstrated that ribavirin showed antiviral effects against FMDV in vitro/in vivo. In addition, it was observed that combining the administration of the antiviral agents orally and complementary therapy with vaccines synergistically enhanced antiviral activity and preserved the survival rate and body weight in the experimental animals. Antiviral agents mixed with an adjuvant were inoculated intramuscularly along with the vaccines, thereby inhibiting virus replication after injection and verifying that it was possible to induce early protection against viral infection prior to immunity being achieved through the vaccine. Finally, pigs treated with antiviral agents and vaccines showed no clinical signs and had low virus excretion. Based on these results, it is expected that this combined approach could be a therapeutic and preventive treatment for early protection against FMD.
Output: Synergistic effect of ribavirin and vaccine for protection during early infection stage of foot-and-mouth disease
Motivation: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein-protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. Results: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein-protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding.
Output: Structural bioinformatics SKEMPI 2.0: an updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation
The subgenomic (sg) mRNAs of arteriviruses (order Nidovirales) form a 5-and 3-coterminal nested set with the viral genome. Their 5 common leader sequence is derived from the genomic 5-proximal region. Fusion of sg RNA leader and "body" segments involves a discontinuous transcription step. Presumably during minusstrand synthesis, the nascent RNA strand is transferred from one site in the genomic template to another, a process guided by conserved transcription-regulating sequences (TRSs) at these template sites. Subgenomic RNA species are produced in different but constant molar ratios, with the smallest RNAs usually being most abundant. Factors thought to influence sg RNA synthesis are size differences between sg RNA species, differences in sequence context between body TRSs, and the mutual influence (or competition) between strand transfer reactions occurring at different body TRSs. Using an Equine arteritis virus infectious cDNA clone, we investigated how body TRS activity affected sg RNA synthesis from neighboring body TRSs. Flanking sequences were standardized by head-to-tail insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of sg RNA abundance, progressively favoring smaller RNA species, was observed. Disruption of body TRS function by mutagenesis did not have a significant effect on the activity of other TRSs. However, deletion of body TRS-containing regions enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from downstream TRSs. The results of this study provide considerable support for the proposed discontinuous extension of minus-strand RNA synthesis as a crucial step in sg RNA synthesis.
Output: Regulation of Relative Abundance of Arterivirus Subgenomic mRNAs
Background: This study examined the effectiveness of a theoretical framework that integrates self-determination theory (SDT) and the theory of planned behavior (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong Kong older adults. Methods: Data were collected at two time points in the winter in Hong Kong, during which influenza is most prevalent. At Time 1, older adults (N = 141) completed self-report measures of SDT (perceived autonomy support from senior center staff, autonomous motivation for influenza prevention) and TPB (attitude, subjective norm, perceived behavioral control, and intention for influenza prevention) constructs with respect to facemask used to prevent infection. Two weeks later, at Time 2, participants' acceptance of a facemask to prevent influenza in the presence of an experimenter with flu-like symptoms was recorded. Results: Path analysis found that perceived autonomy support of senior center staff was positively and significantly linked to autonomous motivation for facemask use, which, in turn, was positively related to intentions to wear facemasks through the mediation of attitude, subjective norm, and perceived behavioral control. However, the effect of intention on facemask use was not significant. Conclusions: Results generally support the proposed framework and the findings of previous studies with respect to intention, but the non-significant intention-behavior relationship may warrant future research to examine the reasons for older adults not to wear facemasks to prevent seasonal influenza despite having positive intentions to do so.
Output: The process by which perceived autonomy support predicts motivation, intention, and behavior for seasonal influenza prevention in Hong Kong older adults
Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administrationapproved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-c production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-jB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases.
Output: Antihelminthic niclosamide modulates dendritic cells activation and function
Children with malignancies or those who are hematopoietic stem cell transplant (HSCT) recipients are at increased risk for healthcare-associated infections (HAI) due to their underlying diagnoses as well as the receipt of immunosuppressive medications that are part of their treatment. In addition, frequent visits to healthcare settings increase the risk for exposure to resistant organisms. Thus, while adherence to infection control and prevention measures recommended for all hospitalized children is essential, additional interventions to reduce the inherent risk of morbidity associated with HAIs are warranted in this special population. There are various factors which contribute to the increased susceptibility to infections in pediatric hematology/oncology (PHO) and HSCT patients, most prominent of them being disruption of cutaneous and mucosal barriers (oral, gastrointestinal, etc.), microbial gastrointestinal translocation, defects in cell-mediated immunity, and insufficient quantities and inadequate function of phagocytes. Goals of infection control and prevention in this population are based on mitigating the risk inherent with the underlying malignancy and associated treatments (i.e., chemotherapy,
Output: 6 Infection Prevention in Pediatric Oncology and Hematopoietic Stem Cell Transplant Recipients Infection Prevention in Pediatric Oncology Patients and Hematopoietic Stem Cell Transplant Recipients
BACKGROUND: Acute respiratory infections (ARI) are one of the prevalent pediatric diseases. Coinfections of respiratory viruses and atypical bacterial respiratory pathogens are common. This study aimed to determine the prevalence of co-infection between respiratory pathogens including viruses, bacteria and atypical bacteria in a sample of Egyptian children presenting with symptoms of acute respiratory tract infection. This one-year prospective cohort study conducted in Abo El Rish Pediatric Hospital, Cairo University over one year included children presenting with symptoms of acute respiratory infection. Enrolled children were subjected to nasopharyngeal swabs or throat swabs and then processed to detect viral, bacterial and atypical bacterial causative agents by culture), retrotranscription polymerase, Monoplex polymerase chain reaction (PCR) and Multiplex PCR. RESULTS: Viral etiological agents were detected in 20 cases (20.8%), while 76 patients (79.2%) had no definite viral aetiology. The most abundant virus detected was Rhinovirus in 36 (27.3%), followed by 21 (15.9%) were positive for RSV, 12 (9.1%) were positive for HMPV, 6 (4.5%) were positive for adenovirus and 3 (2.3%) were positive for influenza B. For Atypical bacterial causes Mycoplasma were positive for 9 (6.8%) cases and one case was positive for Bordetella parapertussis. Viral and atypical bacteria Co infection were detected in 14 (10.6%) of cases. These results suggest that coinfection with bacteria or atypical bacteria in children with acute respiratory tract infection is common and this co-infection can induce serious illness. The multiplex reversetranscriptase polymerase chain reaction should become an essential tool for epidemiological studies and can fill the gap between clinical presentation and definitive diagnosis.
Output: Respiratory Viruses and Atypical Bacteria Co-Infection in Children with Acute Respiratory Infection
Due to its excessively high capacity for human-to-human transmission, the 2019 novel coronavirus disease , first reported in Wuhan in China, spread rapidly to the entire nation and beyond, and has now been declared a global public health emergency. Understanding the transmission pattern of the virus and the efficacy of transmission control measures is crucial to ensuring regional and global disease control. Here we propose a simple model based on exponential infectious growth, but with a timevarying, largely damping, transmission rate. This model provides an excellent fit to the existing data from the 102 countries and regions which have reported cases for more than 6 days, and, we think, has largely captured the transmission patterns of the COVID-19 outbreak under a variety of intervention and control measures. We found that the damping rate, defined as the rate of the exponential decline in transmission rate, ranged from -0.125 to 0.513 d -1 globally (a negative damping rate represents acceleration in spread). The estimated peak time (when the fastest spread occurs) and the final number of infections were found to be greatly affected by the damping rate. Successful control measures, such as those implemented in China and South Korea, have resulted in a clear pattern of exponential damping in the viral spread (also shown during the 2003 outbreak of Severe Acute Respiratory Syndrome, SARS). The damping rate, therefore, could be used as an indicator for the efficacy of implemented control measures. Our model suggests that the COVID-19 outbreak is currently accelerating worldwide, especially rapidly in certain countries (e.g. USA and Australia) where exponential damping is yet to emerge. Consistent with the message from the World Health Organisation (WHO), we thus strongly suggest all countries to take active measures to contain this global pandemic. Slight increments in the damping rate from additional control efforts, especially in countries showing weak or no exponential damping in COVID-19 transmission, could lead to a radically more positive outcome in the fight to contain the pandemic.
Output: Exponential damping: The key to successful containment of COVID-19
We determined the interferon-␥ (IFN-␥) cDNA sequence from three porcine breeds, Duroc, Landrance/Duroc hybrid, and Landrance breeds. Five single nucleotide polymorphisms (SNPs) of porcine IFN-␥ (PoIFN-␥) were identified, respectively, at positions 269 (A/G), 376 (C/T), 426 (T/C), and 465 (T/C) of the coding sequence in Landrance/Duroc hybrid, and at position 251 (A/G) in Landrance breed. Among them, A269G and A251G polymorphisms resulted in Q67R and K61R replacements in the mature protein. PoIFN-␥ cDNAs of Duroc breed (PoIFN-␥-W) and Landrance/Duroc hybrid (PoIFN-␥-M), which, respectively, encoded Q67 and R67, were introduced into a prokaryotic expression vector pET32 to express recombinant PoIFN-␥-W (rPoIFN-␥-W) and rPoIFN-␥-M protein variants in Escherichia coli. The identity of both protein variants was further confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We then compared bioactivities of these two recombinant proteins. Although both recombinant protein variants exhibited comparable activities in antiproliferation of PK-15 cells and in nitric oxide (NO) induction of porcine peripheral monocytes, antiviral activity of rPoIFN-␥-W protein was significantly higher (P < 0.001) than that of rPoIFN-␥-M protein in a plaque inhibition assay using pseudorabies virus (PRV). IC50 values of rPoIFN-␥-W and rPoIFN-␥-M protein in anti-PRV assay were determined as 5.3 ± 1.3 and 9.3 ± 4.3 nM, respectively. In conclusion, we have identified five novel SNPs in PoIFN-␥ cDNA, including two missense polymorphisms that result in Q67R and K61R replacements. Our results further demonstrate that Q67R can markedly reduce antiviral activity of the PoIFN-␥ protein. This is the first report that shows the functional SNP in the coding region of IFN-␥. In the future, it is imperative to determine whether Q67R replacement in IFN-␥ may have disease association.
Output: A missense polymorphism in porcine interferon-␥ cDNA affects antiviral activity of the protein variant
Pneumonia is one of the most common causes of death from infectious diseases worldwide, and the most common fatal infection acquired in hospitals. Despite advances in prevention strategies, such as antibiotic therapies and intensive care, significant improvement in the mortality rate is still lacking. This high mortality is largely due to the limitations in current clinical practices and laboratory tests, which delay the timing of adequate antibiotic therapy. In recent years, many indicators (biomarkers) are present in scenarios where infectious pathogens invade into the body. These biomarkers, as reflected in specific biological responses to infections, have been reported to demonstrate the ability to facilitate the diagnosis, risk stratification, and management of pneumonia. This review provides a schematic overview of these new potential biomarkers based on the categories of (1) microorganisms and their derivatives, (2) inflammation mediators, (3) inflammation response proteins, and (4) stress-sensing proteins. In addition, approaches to identifying new biomarkers are also briefly introduced. Although no current biomarker can solely achieve a definitive diagnosis, many of them can be complemented, rather than replaced outright, in routine clinical practices to improve decision-making processes regarding pneumonia.
Output: New markers in pneumonia
Motivated by the rapid upsurge of COVID-19 cases in the United States beginning March 2020, we forecast the disease spread and assess the effectiveness of containment strategies by using an estalished network-driven epidemic dynamic model. Our model is initialized using the daily counts of active and confirmed COVID-19 cases across the US. Based on our model predictions for the March 14-16 timeframe, the national epidemic peak could be expected to arrive by early June, corresponding to a daily active count of ≈ 7% of the US population, if no containment plans are implemented. Epidemic peaks are expected to arrive in the states of Washington and New York by May 21 and 25, respectively. With a modest 25% reduction in COVID-19 transmissibility via community-level interventions, the epidemic progression could be delayed by up to 34 days. Wholesale interstate traffic restriction is ineffective in delaying the epidemic outbreak, but it does desynchronize the arrival of state-wise epidemic peaks, which could potentially alleviate the burden on limited available medical resources. In addition to forecasting the arrival timeline of the state-wise epidemic peaks, we attempt at informing the optimal timing necessary to enforce community-level interventions. Our findings underscore the pressing need for preparedness and timely interventions in states with a large fraction of the vulnerable uninsured and liquid-asset-poverty populations.
Output: Title: COVID-19 Progression Timeline and Effectiveness of Response-to-Spread Interventions across the United States
Conidiobolomycosis is a rare fungal disease of both humans and animals, occurring mainly in tropical and subtropical climates. We describe a disseminated fungal infection in a young, apparently immunocompetent dog who initially presented for antibiotic resistant pneumonia. Histopathology and mycology identified a Conidiobolus sp., further confirmed as Conidiobolus incongruus through DNA sequencing of D1/D2 regions. This is the first report of this species causing disease in dogs and the fifth reported infection in animals.
Output: Disseminated Conidiobolus incongruus in a dog: A case report and literature review
To determine whether specific asparaginelinked (N-linked) oligosaccharides present in cell surface glycoproteins are required for cell-cell interactions within the peripheral nervous system, we have used castanospermine to inhibit maturation of N-linked sugars in cell cultures of neurons or neurons plus Schwann cells. Maximally 10-15 % of the N-linked oligosaccharides on neuronal proteins have normal structure when cells are cultured in the presence of 250 lxg/ml castanospermine; the remaining oligosaccharides are present as immature carbohydrate chains not normally found in these glycoproteins. Although cultures were treated for 2 wk with castanospermine, cells always remained viable and appeared healthy. We have analyzed several biological responses of embryonic dorsal root ganglion neurons, with or without
Output: Specific Asparagine-linked Oligosaccharides Are Not Required for Certain Neuron-Neuron and Neuron-Schwann Cell Interactions
The cancer burden is a global problem, and oncology nurses should be accountable for delivering safe and effective cancer care and providing the best possible experience for patients. The development and application of evidence-based practice in cancer care is an effective strategy in achieving this goal; however, the journey in which such practice involves may encounter various challenges. In this article, the author discusses her own experience, successful and unsuccessful of such a journey. Both challenges and opportunities are identified, and suggestions put forward for making collaborative efforts.
Output: Evidence-Based Practice in Cancer Care Asia-Pacifi c
Next generation sequencing (NGS) is a powerful tool for the characterization, discovery, and molecular identification of RNA viruses. There were multiple NGS library preparation methods published for strand-specific RNA-seq, but some methods are not suitable for identifying and characterizing RNA viruses. In this study, we report a NGS library preparation method to identify RNA viruses using the Ion Torrent PGM platform. The NGS sequencing adapters were directly inserted into the sequencing library through reverse transcription and polymerase chain reaction, without fragmentation and ligation of nucleic acids. The results show that this method is simple to perform, able to identify multiple species of RNA viruses in clinical samples.
Output: Next-generation sequencing library preparation method for identification of RNA viruses on the Ion Torrent Sequencing Platform