niryuu/sni-each-converted huggingface dataset:
The clinical importance and efficacy of facemasks in infection prevention have been documented in the international literature. Past studies have shown that the perceived susceptibility, the perceived severity of being afflicted with life-threatening diseases, and the perceived benefits of using a facemask are predictors of a person's use of a facemask. However, I argue that people wear a facemask not merely for infection prevention, and various sociocultural reasons have been motivating people to wear (and not wear) a facemask. Facemasks thus have sociocultural implications for people. Research on the sociocultural meanings of facemasks is scant, and even less is known on how the shifting sociocultural meanings of facemasks are related to the changing social environment, which, I argue, serve as remarkable underlying factors for people using (and not using) facemasks. As new infectious diseases such as avian influenza and Middle East Respiratory Syndrome have been emerging, threatening people's health worldwide, and because facemasks have been documented to have substantial efficacy in the prevention of infection transmission, understanding the sociocultural meanings of facemasks has significant implications for public health policymakers and health care providers in designing a socially and culturally responsive public health and infection control policy for the community. Methods: A qualitative research design involving the use of 40 individual, in-depth semistructured interviews and a phenomenological analysis approach were adopted. Results: The sociocultural meanings of the facemask have been undergoing constant change, from positive to negative, which resulted in the participants displaying hesitation in using a facemask in the post-SARS era. Because it represents a violation of societal ideologies and traditional Chinese cultural beliefs, the meanings of the facemask that had developed during the SARS outbreak failed to be sustained in the post-SARS era. Conclusion: The changes in meaning not only influenced the participants' perceptions of the facemask but also influenced their perceptions of people who use facemasks, which ultimately influenced their health behavior, preventing them from using facemasks in the post-SARS era. These findings have critical implications for designing a culturally responsive infection prevention and facemask usage policy in the future.
Output: Qualitative study on the shifting sociocultural meanings of the facemask in Hong Kong since the severe acute respiratory syndrome (SARS) outbreak: implications for infection control in the post-SARS era
Nevertheless, its antivirus evidence in animal studies is not satisfactory, which might be due to the lack of appropriate animal model. Previously, we had utilized restraint stress to establish mouse H1N1 susceptibility model which was helpful in evaluating the anti-virus effect of medicines targeting host factors, such as type I interferon production. In this study, this model was employed to investigate the effect and mechanism of indirubin, a natural bisindole alkaloid from Isatis indigotica, on influenza A virus susceptibility. In the in vitro study, the stress hormone corticosterone was used to simulate restraint stress. Our results demonstrated that indirubin decreased the susceptibility to influenza virus with lowered mortality and alleviated lung damage in restraint-stressed mice model. Moreover, indirubin promoted the expression of interferon-β and interferon inducible transmembrane 3. In addition, indirubin maintained the morphology and function of mitochondria following influenza A virus infection. Further study revealed that indirubin promoted interferon-β production through promoting mitochondrial antiviral signaling pathway. Our study indicated that indirubin could be a candidate for the therapy of influenza.
Output: Indirubin, a bisindole alkaloid from Isatis indigotica, reduces H1N1 susceptibility in stressed mice by regulating MAVS signaling
The People's Republic of China increasingly has turned to political warfare and sharp power to influence U.S. policy toward China and on international issues that it considers important. This turn in part reflects the limited effectiveness of Beijing's much-increased hard power and its never-formidable and now-reduced soft power as means to achieve China's ends with the United States. China's political warfare and uses of sharp power pursue both direct influence on U.S. policy and indirect impact through affecting American attitudes toward China and China-related issues. China's efforts range across many sectors-including business, culture, media, education, and more-and they have prompted reactions and countermeasures. In China's view, the United States has long been engaged in something like political warfare or sharp power undertakings targeting China. If, or as, U.S.-China relations continue to become more adversarial, political warfare, uses of sharp power, and measures to counter them are likely to increase.
Output: Spring 2020 | 1
Bovine respiratory disease complex is a major cause of illness in dairy calves. The diagnosis of active infection of the lower respiratory tract is challenging on daily basis in the absence of accurate clinical signs. Clinical scoring systems such as the Californian scoring system, are appealing but were developed without considering the imperfection of reference standard tests used for case definition. This study used a Bayesian latent class model to update Californian prediction rules. The results of clinical examination and ultrasound findings of 608 preweaned dairy calves were used. A model accounting for imperfect accuracy of thoracic ultrasound examination was used to obtain updated weights for the clinical signs included in the Californian scoring system. There were 20 points (95% Bayesian credible intervals: 11-29) for abnormal breathing pattern, 16 points (95% BCI: 4-29) for ear drop/head tilt, 16 points (95% BCI: 9-25) for cough, 10 points (95% BCI: 3-18) for the presence of nasal discharge, 7 points (95% BCI: −1 to 8) for rectal temperature ≥39.2°C, and −1 points (95% BCI: −9 to 8) for the presence of ocular discharge. The optimal cut-offs were determined using the misclassification cost-term term (MCT) approach with different possible scenarios of expected prevalence and different plausible ratio of false negative costs/false positive costs. The predicted probabilities of active infection of the lower respiratory tract were also obtained using posterior densities of the main logistic regression model. Depending on the context, cut-off varying from 9 to 16 can minimized the MCT. The optimal cut-off decreased when expected prevalence of disease and false negative/false positive ratio increased.
Output: Validation of a clinical scoring system for bovine respiratory disease complex diagnosis in preweaned dairy calves using a Bayesian framework
Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H + -ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.
Output: Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects
Background: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. Results: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses.
Output: BMC Genomics Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes epidemic fever, rash and polyarthralgia in Africa and Asia. Although it is known since the 1950s, new epidemiological and clinical features reported during the recent outbreak in the Indian Ocean can be regarded as the emergence of a new disease. Numerous severe forms of the infection have been described that put emphasis on the lack of efficient antiviral therapy. Among the virus-encoded enzymes, nsP2 constitutes an attractive target for the development of antiviral drugs. It is a multifunctional protein of approximately 90 kDa with a helicase motif in the N-terminal portion of the protein while the papain-like protease activity resides in the C-terminal portion. The nsP2 proteinase is an essential enzyme whose proteolytic activity is critical for virus replication. In this work, a recombinant CHIKV nsP2pro and a C-terminally truncated variant were expressed in Escherichia coli and purified by metal-chelate chromatography. The enzymatic properties of the proteinase were then determined using specific synthetic fluorogenic substrates. This study constitutes the first characterization of a recombinant CHIKV nsP2 cysteine protease, which may be useful for future drug screening.
Output: Expression and biochemical characterization of nsP2 cysteine protease of Chikungunya virus
Feline and primate immunodeficiency viruses (FIVs, SIVs, and HIV) are transmitted via direct contact (e.g. fighting, sexual contact, and mother-offspring transmission). This dynamic likely poses a behavioral barrier to cross-species transmission in the wild. Recently, several host intracellular anti-viral proteins that contribute to species-specificity of primate lentiviruses have been identified revealing adaptive mechanisms that further limit spread of lentiviruses between species. Consistent with these interspecies transmission barriers, phylogenetic evidence supports the prediction that FIV transmission is an exceedingly rare event between free-ranging cat species, though it has occurred occasionally in captive settings. Recently we documented that puma and bobcats in Southern California share an FIV strain, providing an opportunity to evaluate evolution of both viral strains and host intracellular restriction proteins. These studies are facilitated by the availability of the 2Â cat genome sequence annotation. In addition, concurrent viral and host genetic analyses have been used to track patterns of migration of the host species and barriers to transmission of the virus within the African lion. These studies illustrate the utility of FIV as a model to discover the variables necessary for establishment and control of lentiviral infections in new species. Published by Elsevier B.V.
Output: Mini review FIV cross-species transmission: An evolutionary prospective
Background: Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms. Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [MRPS7]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [HIRP5]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between Bestkeeper© and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology. Conclusion: Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present.
Output: BMC Molecular Biology Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.
Output: Lipid-Based Particles: versatile Delivery Systems for Mucosal vaccination against infection
Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics.
Output: A Reverse Genetics Platform That Spans the Zika Virus Family Tree
Pulmonary arterial hypertension (PAH) is a chronic lung disease with poor diagnosis and limited therapeutic options. The currently available therapies are ineffective in improving the quality of life and reducing mortality rates. There exists a clear unmet medical need to treat this disease, which necessitates the discovery of novel therapeutic targets/agents for safe and successful therapy. An altered renin-angiotensin system (RAS) has been implicated as a causative factor in the pathogenesis of PAH. Angiotensin II (Ang II), a key effector peptide of the RAS, can exert deleterious effects on the pulmonary vasculature resulting in vasoconstriction, proliferation, and inflammation, all of which contribute to PAH development. Recently, a new member of the RAS, angiotensin converting enzyme 2 (ACE2), was discovered. This enzyme functions as a negative regulator of the angiotensin system by metabolizing Ang II to a putative protective peptide, angiotensin-(1-7). ACE2 is abundantly expressed in the lung tissue and emerging evidence suggests a beneficial role for this enzyme against lung diseases. In this review, we focus on ACE2 in relation to pulmonary hypertension and provide proof of principle for its therapeutic role in PAH.
Output: ACE2, a promising therapeutic target for pulmonary hypertension
Advances in cancer therapy have focused attention on the quality of life of cancer survivors. Since infertility is a major concern following chemotherapy, it is important to characterize the drug-specific damage to the reproductive system to help find appropriate protective strategies. This study investigates the damage on neonatal mouse ovary maintained in vitro for 6 days, and exposed for 24 h (on Day 2) to clinically relevant doses of Docetaxel (DOC; low: 0.1 mM, mid: 1 mM, high: 10 mM). Furthermore, the study explores the putative protective action exerted by Tri-iodothyronine (T3; 10 27 M). At the end of culture, morphological analyses and follicle counts showed that DOC negatively impacts on early growing follicles, decreasing primary follicle number and severely affecting health at the transitional and primary stages. Poor follicle health was mainly due to effects on granulosa cells, indicating that the effects of DOC on oocytes were likely to be secondary to granulosa cell damage. DOC damages growing follicles specifically, with no direct effect on the primordial follicle reserve. Immunostaining and western blotting showed that DOC induces activation of intrinsic, type II apoptosis in ovarian somatic cells; increasing the levels of cleaved caspase 3, cleaved caspase 8, Bax and cleaved poly(ADP-ribose) polymerase, while also inducing movement of cytochrome C from mitochondria into the cytosol. T3 did not prevent the damage induced by the low dose of DOC. These results demonstrated that DOC induces a gonadotoxic effect on the mouse ovary through induction of somatic cell apoptosis, with no evidence of direct effects on the oocyte, and that the damaging effect is not mitigated by T3.
Output: Docetaxel induces moderate ovarian toxicity in mice, primarily affecting granulosa cells of early growing follicles
State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered Pichia pastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored "bait" Fc, which results in targeting functional "half" IgGs to the cell wall of Pichia pastoris without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered Pichia pastoris, this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle.
Output: Monoclonal Antibodies in Glyco-Engineered Pichia pastoris
Background: Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS) is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises. Methods: This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as < 40%; intermediate as 41-70%; high as 71-100% of the maximum score of 192. Descriptive statistics, T-test, and Univariate Analysis of Variance were used. Results: None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19) of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04). Conclusions: The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied.
Output: Hospital incident command system (HICS) performance in Iran; decision making during disasters
A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Afri ca, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., αdystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.
Output: Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever
An epizootic of feline infectious peritonitis in a captive cheetah population during 1982-1983 served to focus attention on the susceptibility of the cheetah (Acinoyx jubatus) to infectious disease. Subsequent observations based upon seroepidemiological surveys and electron microscopy of fecal material verified that cheetahs were indeed capable of being infected by coronaviruses, which were antigenically related to coronaviruses affecting domestic cats, i.e. feline infectious peritonitis virus/feline enteric coronavirus. Coincident with the apparent increased susceptibility of the cheetah to infectious diseases, were observations that the cheetah was genetically unusual insofar as large amounts of enzyme-encoding loci were monomorphic, and that unrelated cheetahs were capable of accepting allogenic skin grafts. These data provided the basis for a hypothesis that the cheetah, through intensive inbreeding, had become more susceptible to viral infections as a result of genetic homogeneity.
Output: Biological and pathological consequences of feline infectious peritonitis virus infection in the cheetah Brief Review
increasing research has demonstrated that expression of brain and muscle arnT-like 1 (BMal1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMal1 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMScs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMal1 in osteogenic differentiation of BMScs. The cell counting Kit-8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), runX family transcription factor 2 (runX2), alkaline phosphatase (alP), osteocalcin (oc) and BMal1 in BMScs was evaluated by reverse transcription-quantitative Pcr and western blotting. alP and alizarin red S (arS) staining were also performed. icariin promoted BMSc proliferation, and upregulated expression of osteogenic genes and BMal1. in addition, expression of the osteogenic genes BMP2, runX2, alP and oc were upregulated by BMal1 overexpression. Furthermore, we confirmed that BMal1 deficiency suppressed osteogenic differentiation in BMScs. Finally, arS staining of BMal1 -/-BMScs revealed that BMal1 was an essential intermediary in matrix mineralization during osteogenic differentiation. in conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMal1-BMP2 signaling in BMScs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.
Output: Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness. Differentially expressed genes which were positively correlated with viral fitness activate hormone-and RNA silencing-mediated pathways of plant defense. In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development. Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts.
Output: Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host's Transcriptome: The Tobacco Etch Potyvirus-Tobacco Case Study
In 2012, a novel coronavirus, initially named as human coronavirus EMC (HCoV-EMC) but recently renamed as Middle East respiratory syndrome human coronavirus (MERS-CoV), was identified in patients who suffered severe acute respiratory infection and subsequent renal failure that resulted in death. Ongoing epidemiological investigations together with retrospective studies have found 61 laboratory-confirmed cases of infection with this novel coronavirus, including 34 deaths to date. This novel coronavirus is culturable and two complete genome sequences are now available. Furthermore, molecular detection and indirect immunofluorescence assay have been developed. The present paper summarises the limited recent advances of this novel human coronavirus, including its discovery, genomic characterisation and detection. HCoV-EMC, MERS-CoV, genomic characterisation, molecular detection Geng H Y, Tan W J. A novel human coronavirus: Middle East respiratory syndrome human coronavirus.
Output: SCIENCE CHINA SPECIAL TOPIC: Haunted with and hunting for viruses A novel human coronavirus: Middle East respiratory syndrome human coronavirus
RNA silencing, including RNA interference, is a novel method of gene regulation and one of the potent host-defense mechanisms against the viruses. In the course of evolution, the viruses have encoded proteins with the potential to suppress the host RNA silencing mechanism as a counterdefense strategy. The virus-encoded RNA silencing suppressors (RSSs) can serve as important biological tools to dissect the detailed RNA silencing pathways and also to evolve the antiviral strategies. Screening and identification of the RSSs are indeed of utmost significance in the field of plant biotechnology. We describe two Green Fluorescent Protein (GFP) reporter-based plant assay systems that rely on two different principles, namely reversal of silencing and enhancement of rolling circle replication (RCR) of geminiviral replicon. These proof-of-concept examples and assay systems could be used to screen various plant, animal, and insect viral ORFs for identification of the RSS activities.
Output: Screening and Identification of Virus-Encoded RNA Silencing Suppressors
Objective: Effective airway management requires both proper technique and the appropriate devices. With the widespread implementation of advanced life-support techniques in emergency medical services (EMS), orotracheal intubation is now performed not only by professional practitioners but, in many occasions, nonprofessionals. With extensively diversified skill equipped, we tested whether the Sunscope, a patented tracheal intubation device with a digital display, is able to facilitate tracheal intubation by naïve EMS personnel with various training backgrounds. Methods: We conducted a study to determine rate of success and time required to insert an orotracheal tube into a mannequin using Sunscope. The participants were placed into the professional group (i.e., anesthesiologists and emergency medical paramedics; EMT-P) or the nonprofessional group (i.e., emergency medical technicians; EMT). Intubation required three steps: equipment preparation, vocal cord exposure, and tube insertion. The time required for each step was recorded by a senior staff member, and the data were analyzed by nonparametric statistics. Results: Each consecutive step in the operating procedure was significantly shorter for the professional group in comparison with the nonprofessional group during the first trial: equipment preparation, 10.5 AE 2.1 vs. 11.9 AE 4.1 seconds; vocal cord exposure, 7.4 AE 7.7 vs. 12.2 AE 7.7 seconds; tube insertion, 8.8 AE 4.8 vs. 17.6 AE 9.4 seconds; and total time required for intubation, 26.7 AE 8.8 vs. 35.8 AE 19.6 seconds. The professional practitioners showed no significant improvement, in terms of time reduction, on the following three trials. On the other hand, the nonprofessional practitioners showed no significant differences, in terms of time required to expose the vocal cords and total operation time, following the third trial in comparison with the professional practitioners. Conclusion: Our research demonstrates that professional practitioners are able to use the Sunscope on their first attempt. Despite a lack of training in conventional endotracheal intubation, emergency medical technicians (EMT-I and -II) were able to complete intubation on their first attempt; a significant reduction in the time required to intubate was noted after repeated practice. All levels of naïve EMTs were able to readily visualize the vocal cords through Sunscope and, thereby, reliably insert the endotracheal tube in less than 1 minute, regardless of their skills before testing.
Output: Original Article
Background The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small-medium cities and rural areas. Objectives To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. Methods Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. Of the 2025 children enrolled in the study, 971 (48Á0%) were positive for at least one viral pathogen, in which 890 (91Á7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35Á8%), respiratory syncytial virus (RSV; 30Á5%) and human rhinovirus (HRV; 21Á5%). Co-infections were found in 302 cases (31Á1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in coinfection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. Conclusions This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong.
Output: A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China
Dendritic cells (DC)-derived or tumor-derived exosomes are a population of nanometer sized membrane vesicles that can induce specific anti-tumor immunity. However, the immunogenic potential and efficiency of exosomes-based tumor vaccine are not satisfactory enough to achieve a curative effect in clinical trials. In this article we investigated whether IL-18 genetic modification of tumor cells can increase the efficacy of exosomes derived from IL-18 gene-modified tumor cells. We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells. We found that Exo/IL-18 naturally contain CEA and bioactive IL-18. Moreover, Exo-IL-18 are potent in chemoattracting DC and T cells, enhancing the proliferation and Th1 cytokine release of PBMC, and promoting the phenotypic and functional maturation of DC. Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8 + CTL from the PBMC of HLA-A*0201 CEA + cancer patients in vitro. In almost all of these experiments, Exo/IL-18 show more potent functions than the conventionally prepared exosomes derived from parent tumor cells without IL-18 gene modification. Our findings suggest that Exo/IL-18 has more potent capability to induce specific anti-tumor immunity, and our strategy of IL-18 modification of exosomes is a feasible approach to develop exosomesbased tumor vaccines.
Output: Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8 + CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells
The objective of the present study was to determine if chicken melanoma differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus (IBDV) infection to initiate and amplify an innate immune response in the chicken MDA5 (chMDA5) signaling pathway. Chicken embryo fibroblast DF-1 cells were infected with IBDV LP1 at a multiplicity of infection (MOI) of 0.5 or 10. In addition, knockdown and overexpression of chMDA5 were performed by transfecting DF-1 cells with chMDA5targeting small interfering RNA (siRNA) or chMDA5expressing DNA. The transfected cells were infected with IBDV LP1 at an MOI of 10. Cell culture supernatants and lysates were collected at 2, 8, 16 and 24 hours postinfection (hpi) for IBDV titer determination and RNA extraction, respectively. IBDV RNA loads and mRNA expression levels of chicken MDA5, interferon-b (IFN-b) promoter stimulator 1 (IPS-1), interferon regulatory factor-3 (IRF-3), IFN-b, double-stranded RNA-dependent protein kinase (PKR), 2 0 ,5 0 -oligoadenylate synthetase (OAS), myxovirus resistance gene (Mx), and major histocompatibility complex class I (MHC class I) were determined by real-time RT-PCR. The IBDV titer increased up to 1.4 9 10 7 plaqueforming units (PFU)/mL at 24 hpi, and the IBDV RNA load reached 464 ng/lL at 24 hpi. The mRNA expression levels of chicken MDA5, IRF-3, IFN-b, PKR, OAS, Mx and MHC class I in IBDV-infected DF-1 cells exhibited significant (p \ 0.05) upregulation up to 906-, 199-, 26,310-, 12-, 66,144-, 64,039-and 33-fold, respectively. Expressed chMDA5 from transfection and double-stranded RNA from IBDV infection were localized or colocalized in the cytoplasm of DF-1 cells at 16 hpi. When chMDA5 was knocked down in DF-1 cells, IBDV titers and RNA loads were significantly higher (p \ 0.05) than those in DF-1 cells without chMDA5 knockdown at 24 hpi. The expression levels of chicken MDA5, IRF-3, IFN-b and MHC class I in chMDA5-knockdown DF-1 cells were significantly lower (p \ 0.05) at 16 and 24 hpi. DF-1 cells overexpressing chMDA5 by transfection with chMDA5 expressing DNA had significantly lower (p \ 0.05) IBDV titers and RNA loads at 16 and 24 hpi and showed significantly higher (p \ 0.05) expression of chicken MDA5, IRF-3, IFN-b, PKR, OAS, Mx and MHC class I at 2 hpi. The results indicated that chicken MDA5 recognized IBDV infection and that this interaction resulted in the activation of chMDA5-related innate immune genes and upregulation of chicken MHC class I.
Output: Chicken melanoma differentiation-associated gene 5 (MDA5) recognizes infectious bursal disease virus infection and triggers MDA5-related innate immunity
Background: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. Results: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is "Centromere -Class II -Class III -Class I". DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. Conclusions: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species.
Output: The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes
Background: Charcoal burning in a sealed room has recently emerged as the second most common suicide means in Hong Kong, causing approximately 200 deaths each year. As charcoal burning suicide victims have a unique sociodemographic profile (i.e., predominantly economically active men), they may commit suicide at specific times. However, little is known about the temporal patterns of charcoal burning suicides. Methods: Suicide data from 2001 to 2008 on victims of usual working age (20-59) were obtained from the registered death files of the Census and Statistics Department of Hong Kong. A total of 1649 cases of charcoal burning suicide were analyzed using a two-step procedure, which first examined the temporal asymmetries in the incidence of suicide, and second investigated whether these asymmetries were influenced by sex and/or economic activity status. Poisson regression analyses were employed to model the monthly and daily patterns of suicide by economic activity status and sex. Results: Our findings revealed pronounced monthly and daily temporal variations in the pattern of charcoal burning suicides in Hong Kong. Consistent with previous findings on overall suicide deaths, there was an overall spring peak in April, and Monday was the common high risk day for all groups. Although sex determined the pattern of variation in charcoal burning suicides, the magnitude of the variation was influenced by the economic activity status of the victims. Conclusion: The traditional classification of suicide methods as either violent or nonviolent tends to elide the temporal variations of specific methods. The interaction between sex and economic activity status observed in the present study indicates that sex should be taken into consideration when investigating the influence of economic activity status on temporal variations of suicide. This finding also suggests that suicide prevention efforts should be both time-and subgroup-specific.
Output: Temporal patterns of charcoal burning suicides among the working age population in Hong Kong SAR: the influence of economic activity status and sex
The enveloped baculoviras\insect cell system has been used extensively for expression of recombinant proteins, including viral fusion proteins. We tested wiid-tyl~ baculovirus for endogenous fusion protein activity. Syncytia formation, dye transfer, and capacitance chanses were observed after incubating infected Spodopterafrugiperda cells in acidic media, consistent with fusion protein activity. Only a short acidic pulse of 10 s is needed to trisect syncytia formation. Identical results were obtained with recombinant baculovirus. This new ~ys:e,r~ !,_ convenient for studying pH activated ccll~dl fusion. However, using this enveloped virus to study ~he mechanism of recomlHzant fusion proteins rexluires caution. Membrane fusion; Viral fusion; Enveloped virus; Cell-cell fusion; Baculovirus exprer~ion system Published by Elsevier Science Publishers B. It. 92] Volume 304, number 2,3 FEBS LETTERS
Output: Acidic pH induces fusion of cells infected with baculovirus to form syncytia