niryuu/sni-each-converted huggingface dataset:
Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.
Output: The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system NIH Public Access
In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources-Wikipedia, the GDELT Project and the Internet Archive-to quantify populationscale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geo-localized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical epidemic models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks. Data Availability Statement: Data are available from the Zenodo repository (https://doi.org/10. 5281/zenodo.3603916). data, and we compare it with mentions of Zika in US news outlets and TV shows. We also compare the collective attention received by the outbreak with the incidence of Zika reported by the US Centers for Disease Control and Prevention in each state. We find that the attention dynamics was highly synchronized across states, irrespective of the local risk of transmission of the virus. By building a linear regression model, we show that the dynamics of collective attention is highly predictable, even at state level, only based on the national media coverage received by the outbreak. News exposure and collective attention during epidemics PLOS Computational Biology | https://doi.org/10.
Output: The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic
Two primers with the length of 22 bases each and 400 bases apart on the spike protein gene of avian infectious bronchitis virus (IBV) were prepared. Using these primers, the genome RNA from twelve strains of the various serotypes were reverse-transcribed to cDNA and amplified by polymerase chain reaction (PCR). With all strains, 400 base DNA was amplified, indicating that there were no apparent insertions or deletions in this region. However, the amplified DNA showed different cleavage patterns by the restriction enzymes. These 12 strains were classified into 5 groups. The strain typing based on a comparison of the cleavage patterns was consistent with the previous serological typing. This study thus provides a simple and rapid method for typing of IBV.
Output: A new typing method for the avian infectious bronchitis virus using polymerase chain reaction and restriction enzyme fragment length polymorphism
Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation.
Output: High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan
Type I interferons (IFN) play a critical role in the innate immune avant-garde against viral infections. Virtually all viruses have developed means to counteract the induction, signaling or antiviral actions of the IFN circuit. Over 170 different virus-encoded IFN-antagonists from 93 distinct viruses have been described up to now, indicating that most viruses interfere with multiple stages of the IFN response. Although every viral IFN antagonist is unique in its own right, four main mechanisms are employed to circumvent innate immune responses: i) general inhibition of cellular gene expression, and ii) sequestration, iii) proteolytic cleavage or iv) proteasomal degradation of key components of the IFN system. The increasing understanding of how different viral IFN antagonists function has been translated to the generation of viruses with mutant IFN antagonists as potential live vaccine candidates. Moreover, IFN antagonists are attractive targets for inhibition by small-molecule compounds.
Output: Viral tricks to grid-lock the type I interferon system
The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites-all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.
Output: Genetic analysis of complex traits in the emerging Collaborative Cross
Pregnant and postpartum women are considered a population at increased risk of hospitalization of H1N1 infection. We report the case of a young postpartum woman, who developed evidence of respiratory failure reaching the point of requiring intubation due to an H1N1 influenza virus infection two days after a caesarean delivery. We emphasize the diagnosis, management, and the outcome focusing on the question "what the care providers, including obstetric health care workers, ought to know?" Diagnostic and management strategy for pregnant or postpartum women with novel influenza A (H1N1) viral infection and increased awareness amongst patients and health care professionals may result in improved survival.
Output: Case Report H1N1 Influenza Viral Infection in a Postpartum Young Woman Causes Respiratory Failure: What the Care Providers Ought to Know?
Background: We present here the recent update of AMS algorithm for identification of post-translational modification (PTM) sites in proteins based only on sequence information, using artificial neural network (ANN) method. The query protein sequence is dissected into overlapping short sequence segments. Ten different physicochemical features describe each amino acid; therefore nine residues long segment is represented as a point in a 90 dimensional space. The database of sequence segments with confirmed by experiments post-translational modification sites are used for training a set of ANNs. The efficiency of the classification for each type of modification and the prediction power of the method is estimated here using recall (sensitivity), precision values, the area under receiver operating characteristic (ROC) curves and leave-one-out tests (LOOCV). The significant differences in the performance for differently optimized neural networks are observed, yet the AMS 3.0 tool integrates those heterogeneous classification schemes into the single consensus scheme, and it is able to boost the precision and recall values independent of a PTM type in comparison with the currently available state-of-the art methods. The standalone version of AMS 3.0 presents an efficient way to indentify post-translational modifications for whole proteomes. The training datasets, precompiled binaries for AMS 3.0 tool and the source code are available at Additional file 1 Supplementary materials for the publication. Supplementary.xls contains detailed results of training and testing of AMS 3.0 tool in MS Excel file format. Additional file 2 PTM predictor software with training data. PTM_Archive.tar.gz includes the predictor software binaries together with all trained ANNs in tar.gz compressed form.
Output: AMS 3.0: prediction of post-translational modifications
288 cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized importations timeline to assess the rapidity of isolation, and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the upcoming weeks. Time from travel to detection has considerably decreased since the first importation, however 6 cases out of 10 were estimated to go undetected. Countries outside China should be prepared for the possible emergence of several undetected clusters of chains of local transmissions.
Output: Lessons learnt from 288 COVID-19 international cases: importations over time, effect of interventions, underdetection of imported cases
CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133 + ) and CD133-negative cells (LC-CD133 2 ) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133 + displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133 + , unlike LC-CD133 2 , highly coexpressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133 + to form spheres and can further facilitate LC-CD133 + to differentiate into LC-CD133 2 . In addition, knock-down of Oct-4 expression in LC-CD133 + can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133 + can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133 + . Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133 + and malignant lung cancer.
Output: Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells
To assess specific cytotoxic T lymphocytes (CTLs) against Severe acute respiratory syndrome (SARS)-coronavirus, a modified DimerX flow cytometry assay was performed with peripheral blood mononuclear cell (PBMC) from HLA-A2 + SARS-recovered donors at different time points post disease. CD8 + DimerX-S1203 + CTLs were detected in the PBMC from these donors up to 3 months after recovery. The percentages of CD8 + DimerX-S1203 + cells paralleled the numbers of interferon-g-positive spots in an ELISPOT assay using the same antigenic peptide. In conclusion, DimerX-based flow cytometry staining may prove to be a real-time method to screen for CTL directed at epitopes from a newly identified virus. D
Output: Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX HLA-A2:Ig fusion protein
Farm animals are sources of meat, milk and eggs for the humans, and animal health ensures the quality and security of these agricultural and sideline products. The animal raising conditions in livestock stations and poultry houses play vital roles in both animal health and production. One of the major factors affecting raising conditions, relative humidity, has not received much attention even though it is important for animal husbandry. In this review, we summarize the impacts of relative humidity on animal health and welfare to draw attention for its importance in the improvement of animal raising conditions in the future.
Output: ScienceDirect Effects of relative humidity on animal health and welfare
In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas-antimicrobial resistance, food safety, and supply chain integrity-in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats. Brooke Courtney, JD, MPH, is Senior Regulatory Counsel, Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Office of the Commissioner; Katherine C. Bond, ScD, is Director, Office
Output: Regulatory Underpinnings of Global Health Security: FDA's Roles in Preventing, Detecting, and Responding to Global Health Threats
Among the various respiratory viruses infecting human beings, coronaviruses are important pathogens, which usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immunecompromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, and various types of respiratory distress syndrome. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Nevertheless, for almost three decades now, data reported in the scientific literature has also demonstrated that, like it was described for other human viruses, coronaviruses have neuroinvasive capacities since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Neuroinvasive coronaviruses could damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virusinduced neuroimmunopathology) and/or viral replication, which directly induces damage to CNS cells (virus-induced neuropathology). Given all these properties, it has been suggested that these opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of neurologic diseases for which the etiology remains poorly understood. Herein, we present host and viral factors that participate in the regulation of the possible pathogenic processes associated with CNS infection by human coronaviruses and we try to decipher the intricate interplay between virus and host target cells in order to characterize their role in the virus life cycle as well as in the capacity of the cell to respond to viral invasion.
Output: Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis
Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin b1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin b1, and identify c-Cbl as a potential E3 ligase that facilitates this process.
Output: Associated Herpesvirus in Endothelial Cells
Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (M pro ) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting M pro , two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC 50 value of 0.05 μ M and 0.04 μ M respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC 50 value of 0.42 μ M and 0.33 μ M, respectively. The X-ray crystal structures of SARS-CoV-2 M pro in complex with 11a and 11b were determined at 1.5 Å resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of M pro . Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.
Output: Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease
cDNA, synthesized on bovine coronavirus (BCV) genomic RNA templates, could be used to detect very small quantities (i .e . 1 pg) of viral RNA by hybridization with either radioisotopic-labelled or biotinylated recombinant plasmids . Virus was optimally attached to nitrocellulose membranes when spotted in 1 x SSC, whereas 20 x SSC was superior for viral RNA. Denaturation and RNA fixation of both RNA, still encapsidated in virus particles and isolated genomic RNA, was achieved by baking of the blots in vacuum . Virus detection in the supernatant of infected HRT-18 cells was feasible, but improved significantly after proteinase K treatment . No homology was observed between virus cDNA with either plasmid DNA or nucleic acid isolated from non-infected HRT-18 cells . Hybridization with radioisotopic-labelled probes in higher formamide concentrations (up to 60%) increased the detection signals, possibly by reducing reassociation of the probe . Significant detection amplification (30-50 times) was achieved in the case of biotinylated probes by stimulation of hyperpolymer formation on already hybridized target sequences, by additional hybridization with biotinylated pUC-19 . A detection amplification was also obtained when hybridization was done with two probes (pBC-52 and pBC-247), containing non-overlapping viral sequences . Although the detectability was surpassed by biotinylated probes, sensitivity was superior in radioisotopic virus detection .
Output: Biotinylated and radioactive cDNA probes in the detection by hybridization of bovine enteric coronavirus
Background: Cotton blue disease (CBD), an important global cotton crop pathology responsible for major economic losses, is prevalent in the major cotton-producing states of Brazil. Typical CBD symptoms include stunting due to internodal shortening, leaf rolling, intense green foliage, and yellowing veins. Atypical CBD symptoms, including reddish and withered leaves, were also observed in Brazilian cotton fields in 2007. Recently, a Polerovirus named Cotton leafroll dwarf virus (CLRDV) was shown to be associated with CBD. Results: To understand the distribution and genetic diversity of CLRDV in Brazil, we analyzed 23 CBD-symptomatic plants from susceptible cotton varieties originating from five of the six most important cotton-growing states, from 2004-2007. Here, we report on CLRDV diversity in plants with typical or atypical CBD symptoms by comparing viral coat protein, RNA polymerase (RdRp), and intergenic region genomic sequences. The virus had a widespread distribution with a low genetic diversity; however, three divergent isolates were associated with atypical CBD symptoms. These divergent isolates had a CLRDV-related coat protein but a distinct RdRp sequence, and probably arose from recombination events. Based on the taxonomic rules for the family Luteoviridae, we propose that these three isolates represent isolates of a new species in the genus Polerovirus.
Output: Virology Journal Widespread distribution and a new recombinant species of Brazilian virus associated with cotton blue disease
Porcine circovirus type 2 (PCV2) is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome (PMWS) for which no antiviral treatment is available. To exploit the possibility of using RNA interference (RNAi) as a therapeutic approach against the disease, plasmid-borne short hairpin RNAs (shRNAs) were generated to target the PCV2 genome. Transfection of these shRNAs into cultured PK15 cells caused a significant reduction in viral RNA production that was accompanied by inhibiting viral DNA replication and protein synthesis in infected cells. The effect was further tested in vivo in a mouse model that has been developed for PCV2 infection. Mice injected with shRNA before PCV2 infection showed substantially decreased microscopic lesions in inguinal lymph nodes compared to controls. In situ hybridization and immunohistochemical analyses showed that shRNA caused a significant inhibition in the level of viral DNA and protein synthesis detected in the lymph nodes of the treated mice relative to the controls. Taken together, these results indicate that shRNAs are capable of inhibiting PCV2 infection in vitro as well as in vivo and thus may constitute an effective therapeutic strategy for PCV2 infection. D
Output: Inhibition of porcine circovirus type 2 replication in mice by RNA interference
Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations.
Output: Treatment strategies for Middle East respiratory syndrome coronavirus
Background: Advances in molecular laboratory techniques are changing the prospects for the diagnosis of viral infectious diseases. Multiplex polymerase chain reaction assay (multiplex-PCR) can detect dozens of pathogens simultaneously, greatly reducing turnaround time (TAT) and improving detection sensitivity. But as a double-edged sword, due to the high sensitivity of PCR, the type of respiratory specimens is critical to diagnosis. In this work, we performed a head-to-head comparison to evaluate the multiplex-PCR yields between two samples, sputum and flocked oropharyngeal swabs (OPS). Methods: Eleven common respiratory pathogens were tested in hospitalized children< 13 years of age who met the criteria for lower respiratory tract infection by GeXP-based multiplex-PCR of paired OPS and sputum. Results: From January to June 2018, 440 children with paired OPS and sputum were tested. The positive rate was 84% (369/440) for OPS and 88% (386/440) for sputum (p = .007). The frequency of detection of HRV, RSV, Influenza A virus, HMPV, parainfluenza virus, adenovirus, M. pneumoniae, coronavirus, bocavirus and C. pneumoniae in sputa was higher than that of OPSs (all p < .001). Both types of specimens had similarly very good kappa values for most of pathogens, except for Mycoplasma pneumonia (κ = 0.61) and Chlamydia pneumoniae (κ = 0.24). Additionally, 79.3% (349/440) of cases showed consistent results between the two types of samples, and they were significantly younger than patients with inconsistent results (p = .002). Conclusions: Flocked oropharyngeal swabs and sputum performed similarly for the detection of common respiratory pathogens in hospitalized children by multiplex-PCR, except for Mycoplasma pneumoniae and Chlamydia pneumoniae. Young patients are likely to have consistent results between the two specimens.
Output: Comparing the yield of oropharyngeal swabs and sputum for detection of 11 common pathogens in hospitalized children with lower respiratory tract infection
Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy. Cancer cells activate chemoresistant pathways and lead to therapeutic failure for patients with TNBC. Several kinases have been identified as chemoresistant genes. However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood. We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines. The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation. Protein expression and phosphorylation were determined by immunoblotting. The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients. Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T. Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells. Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells. Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC. High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients. Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.
Output: Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells
Background. With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century. Methodology/Principal Findings. We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak. This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R 0 = 4.97, SE = 3.31). Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30-40 days). The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95). Conclusions/Significance. These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases.
Output: Transmissibility of the Influenza Virus in the 1918 Pandemic
Rationale: Respiratory viral infections can result in the establishment of chronic lung diseases. Understanding the early innate immune mechanisms that participate in the development of chronic postviral lung disease may reveal new targets for therapeutic intervention. The intracellular viral sensor protein melanoma differentiation-associated protein 5 (MDA5) sustains the acute immune response to Sendai virus, a mouse pathogen that causes chronic lung inflammation, but its role in the development of postviral chronic lung disease is unknown. Objectives: To establish the role of MDA5 in the development of chronic lung disease.
Output: Deficiency of Melanoma Differentiation-associated Protein 5 Results in Exacerbated Chronic Postviral Lung Inflammation
Microarray hybridization based identification of viral genotypes is increasingly assuming importance due to outbreaks of multiple pathogenic viruses affecting humans causing wide-spread morbidity and mortality. Surprisingly, microarray based identification of food-borne viruses, one of the largest groups of pathogenic viruses, causing more than 1.5 billion infections world-wide every year, has lagged behind. Cell-culture techniques are either unavailable or time consuming for routine application. Consequently, current detection methods for these pathogens largely depend on polymerase chain reaction (PCR) based techniques, generally requiring an investigator to preselect the target virus of interest. Here we describe the first attempt to use the microarray as an identification tool for these viruses. We have developed methodology to synthesize targets for virus identification without using PCR, making the process genuinely sequence independent. We show here that a tiling microarray can simultaneously detect and identify the genotype and strain of common food-borne viruses in a single experiment.
Output: Detection and Identification of Common Food-Borne Viruses with a Tiling Microarray
• Segregated spatial domain and individual-based linkage are incorporated into SIS model. • Activating a small number of individual-based linkage between different spatial domains can prompt the outbreak of epidemic globally. • Narrowing segregated spatial domain and reducing mobility are conducive to suppression of infectious disease. a b s t r a c t By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible-infected-susceptible) model, we propose a generalized epidemic model which can change from the territorial epidemic model to the networked epidemic model. The role of the individual-based linkage between different spatial domains is investigated. As we adjust the timescale parameter τ from 0 to unity, which represents the degree of activation of the individual-based linkage, three regions are found. Within the region of 0 < τ < 0.02, the epidemic is determined by local movement and is sensitive to the timescale τ . Within the region of 0.02 < τ < 0.5, the epidemic is insensitive to the timescale τ . Within the region of 0.5 < τ < 1, the outbreak of the epidemic is determined by the structure of the individual-based linkage. As we keep an eye on the first region, the role of activating the individual-based linkage in the present model is similar to the role of the shortcuts in the two-dimensional small world network. Only activating a small number of the individualbased linkage can prompt the outbreak of the epidemic globally. The role of narrowing segregated spatial domain and reducing mobility in epidemic control is checked. These two measures are found to be conducive to curbing the spread of infectious disease only when the global interaction is suppressed. A log-log relation between the change in the number of infected individuals and the timescale τ is found. By calculating the epidemic threshold * L.-X. Zhong et al. / Physica A 436 (2015) 482-491 483 and the mean first encounter time, we heuristically analyze the microscopic characteristics of the propagation of the epidemic in the present model.
Output: Physica A Coupled effects of local movement and global interaction on contagion
There is increasing evidence that viral infection, expression of viral protein or the presence of viral DNA causes the host cell cycle to arrest during G2/M. The mechanisms used by viruses to cause arrest vary widely; some involve the activation of the cellular pathways that induce arrest in response to DNA damage, while others use completely novel means. The analysis of virus-mediated arrest has not been proven easy, and in most cases the consequences of arrest for the virus life cycle are not well defined. However, a number of effects of arrest are being investigated and it will be interesting to see to what extent perturbation of the G2/M transition is involved in viral infections. Crown
Output: G2/M cell cycle arrest in the life cycle of viruses
Italy is currently experiencing the largest COVID-19 outbreak in Europe so far, with more than 100,000 confirmed cases. Following the identification of the first infections, on February 21, 2020, national authorities have put in place an increasing number of restrictions aimed at containing the outbreak and delaying the epidemic peak. Since March 12, the whole country is under lockdown. Here we provide the first quantitative assessment of the impact of such measures on the mobility and the spatial proximity of Italians, through the analysis of a large-scale dataset on deidentified, geo-located smartphone users. With respect to pre-outbreak averages, we estimate a reduction of 50% of the total trips between Italian provinces, following the lockdown. In the same week, the average users' radius of gyration has declined by about 50% and the average degree of the users' proximity network has dropped by 47% at national level.
Output: COVID-19 outbreak response: a first assessment of mobility changes in Italy following national lockdown
The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine diseases in the world. It is causing an enormous economic burden due to reproductive failure in sows and a complex respiratory syndrome in pigs of all ages, with mortality varying from 2 to 100% in the most extreme cases of emergent highly pathogenic strains. PRRSV displays complex interactions with the immune system and a high mutation rate, making the development, and implementation of control strategies a major challenge. In this review, the biology of the virus will be addressed focusing on newly discovered functions of non-structural proteins and novel dissemination mechanisms. Secondly, the role of different cell types and viral proteins will be reviewed in natural and vaccine-induced immune response together with the role of different immune evasion mechanisms focusing on those gaps of knowledge that are critical to generate more efficacious vaccines. Finally, novel strategies for antigen discovery and vaccine development will be discussed, in particular the use of exosomes (extracellular vesicles of endocytic origin). As nanocarriers of lipids, proteins and nucleic acids, exosomes have potential effects on cell activation, modulation of immune responses and antigen presentation. Thus, representing a novel vaccination approach against this devastating disease.
Output: Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV)
Interferon-inducible p200 family protein IFI204 was reported to be involved in DNA sensing, and subsequently induces the production of type I interferons and proinflammatory mediators. However, its function in the regulation of antiviral innate immune signaling pathway remains unclear. Here we reported a novel role of IFI204 that specifically inhibits the IRF7mediated type I interferons response during viral infection. IFI204 and other p200 family proteins are highly expressed in mouse hepatitis coronavirus-infected bone marrow-derived dendritic cells. The abundant IFI204 could significantly interact with IRF7 in nucleus by its HIN domain and prevent the binding of IRF7 with its corresponding promoter. Moreover, other p200 family proteins that possess HIN domain could also inhibit the IRF7-mediated type I interferons. These results reveal that, besides the positive regulation function in type I interferon response at the early stage of DNA virus infection, the interferon-inducible p200 family proteins such as IFI204 could also negatively regulate the IRF7-mediated type I interferon response after RNA virus infection to avoid unnecessary host damage from hyperinflammatory responses. The regulation of type I interferon signaling pathway is dynamic sequential processes and must be tightly regulated to keep balance between antiviral immune and hyper-inflammatory responses. The precise regulation mechanisms of the innate immune signaling pathway are still worth studying. Here, we found a novel role of the interferon-inducible p200 family protein IFI204 that specifically inhibits the IRF7-mediated type I interferon production by negative control of the transcriptional activity of IRF7 in the nucleus at the late stage of RNA virus infection. Previous studies showed that IFI204 is involved in DNA sensing during DNA virus infection to initiate antiviral immune responses. We demonstrate that IFI204 can inhibit IRF7-mediated activation of type I IFN responses induced by RNA virus infection, which is in contrast with its role in IRF3 activation in cGAS-PLOS Pathogens | https://doi.org/10.
Output: P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus
Background: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, which is a major causative agent of cervical cancer. Cellular transformation is associated with deregulated expression of the E6 and E7 oncogenes. E7 has been shown to bind a number of cellular proteins, including the cell cycle control protein pRb. In this study, RNA aptamers (small, singlestranded oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed as molecular tools to further investigate these protein-protein interactions. This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining). GST-pull down and bead binding assays were used to demonstrate that the binding of A2 required N-terminal residues of E7 known to be involved in interaction with the cell cycle control protein, pRb. Using a similar approach, A2 was shown to disrupt the interaction between E7 and pRb in vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels, as observed by immunoblotting. Conclusions/Significance: This paper includes the first characterisation of the effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis. Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials. In addition to its role as a molecular tool, A2 could have further applications in the future.
Output: An RNA Aptamer Provides a Novel Approach for the Induction of Apoptosis by Targeting the HPV16 E7 Oncoprotein
Background: Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. Methods: The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. Results: Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. Conclusions: Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.
Output: The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus
Aims-The aim of this study was to develop and demonstrate an approach for describing the diversity of human pathogenic viruses in an environmentally isolated viral metagenome. Methods and Results-In silico bioinformatic experiments were used to select an optimum annotation strategy for discovering human viruses in virome datasets, and applied to annotate a class B biosolids virome. Results from the in silico study indicated that less than 1% errors in virus identification could be achieved when nucleotide-based search programs (BLASTn or tBLASTx), viral genome only databases, and sequence reads greater than 200 nt were considered. Within the 51,925 annotated sequences, 94 DNA and 19 RNA sequences were identified as human viruses. Virus diversity included environmentally transmitted agents such as parechovirus, coronavirus, adenovirus, and aichi virus, as well as viruses associated with chronic human infections such as human herpes and hepatitis C viruses. Conclusions-This study provided a bioinformatic approach for identifying pathogens in a virome dataset, and demonstrated the human virus diversity in a relevant environmental sample. Significance and Impact of Study-As the costs of next generation sequencing decrease, the pathogen diversity described by virus metagenomes will provide an unbiased guide for subsequent cell-culture and quantitative pathogen analyses, and ensures that highly enriched and relevant pathogens are not neglected in exposure and risk assessments.
Output: Viral Metagenome Analysis to Guide Human Pathogen Monitoring in Environmental Samples