niryuu/sni-each-converted huggingface dataset:
A mass mortality event involving Chaerephon plicatus and Taphozous theobaldi bats occurred during a heat wave in April 2016 in Cambodia. This was investigated to clarify the causes of the die-off and assess the risk to public health. Field evidences, clinical signs, and gross pathology findings were consistent with a heat stress hypothesis. However, the detection of a novel bat paramyxovirus raises questions about its role as a contributing factor or a coincidental finding. Systematic documentation of bat die-offs related to extreme weather events is necessary to improve understanding of the effect of changing weather patterns on bat populations and the ecosystem services they provide.
Output: Extreme temperature event and mass mortality of insectivorous bats
Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8 ϩ cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral clearance and tissue injury during HCV infection could be involved in the induction of AIH. To explore whether the antiviral cellular immunity may turn against self-antigens, we characterized the primary CTL response against an HLA-A * 0201-restricted HCV-derived epitope, i.e., HCV core 178-187, which shows sequence homology with human CYP2A6 and CYP2A7 8-17. To determine the relevance of these homologies for the pathogenesis of HCV-associated AIH, we used synthetic peptides to induce primary CTL responses in peripheral blood mononuclear cells of healthy blood donors and patients with chronic HCV infection. We found that the naive CTL repertoire of both groups contains cross-reactive CTLs inducible by the HCV peptide recognizing both CYP2A6 and CYP2A7 peptides as well as endogenously processed CYP2A6 protein. Importantly, we failed to induce CTLs with the CYPderived peptides that showed a lower capacity to form stable complexes with the HLA-A2 molecule. These findings demonstrate the potential of HCV to induce autoreactive CD8 ϩ CTLs by molecular mimicry, possibly contributing to virus-associated autoimmunity.
Output: Molecular Mimicry of Human Cytochrome P450 by Hepatitis C Virus at the Level of Cytotoxic T Cell Recognition
The spread of the COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor via which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating : bioRxiv preprint 2 the binding energy between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with the phylogeny analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of human engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.
Output: Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism
Severe inflammation may lead to multiple organs dysfunction syndrome, which has a high mortality. MicroRNA is found participated in this process. In this study we developed a lipopolysaccharide-induced inflammation cell model on macrophages and a lipopolysaccharide-induced inflammation mouse model. It was found that during inflammation, microRNA-9 was increased, accompanied with the up-regulation of pro-inflammatory cytokines and anti-inflammatory cytokines. Down-regulation of microRNA-9 inhibited the up-regulation of inflammatory cytokines, promoted the up-regulation of anti-inflammatory cytokines and induced the remission of organ damage, showing a protective effect in inflammation. Bioinformatics analysis combined with luciferase reporter assay showed that SIRT1 was the target gene of microRNA-9. Transfection of microRNA-9 inhibitor could increase the level of SIRT1 and decrease the activation of NF-κB pathway in macrophages. Myeloid specific sirt1 knockout mice were included and we found that lack of SIRT1 in mice macrophages led to aggravated inflammation, cell apoptosis and organ injury, and eliminated the protective property of microRNA-9 inhibitor. In conclusion, we demonstrated that inhibition of microRNA-9 could alleviate inflammation through the up-regulation of SIRT1 and then suppressed the activation of NF-κB pathway. This is a meaningful explore about the specific mechanism of microRNA-9 in inflammation.
Output: Inhibition of SIRT1 by microRNA-9, the key point in process of LPS-induced severe inflammation
Bacterial coinfections occur in respiratory viral infections, but the attack rates and the clinical profile are not clear. The aim of this study was to determine bacterial coinfections in children hospitalized for acute expiratory wheezing with defined viral etiology. A total of 220 children aged 3 months to 16 years were investigated. The viral etiology of wheezing was confirmed by viral culture, antigen detection, serologic investigation, and/or PCR. Specific antibodies to common respiratory bacteria were measured from acute and convalescent serum samples. All children were examined clinically for acute otitis media, and subgroups of children were examined radiologically for sinusitis and pneumonia. Rhinovirus (32%), respiratory syncytial virus (31%), and enteroviruses (31%) were the most common causative viruses. Serologic evidence of bacterial coinfection was found in 18% of the children. Streptococcus pneumoniae (8%) and Mycoplasma pneumoniae (5%) were the most common causative bacteria. Acute otitis media was diagnosed in 44% of the children. Chest radiographs showed alveolar infiltrates in 10%, and paranasal radiographs and clinical signs showed sinusitis in 17% of the older children studied. Leukocyte counts and serum C-reactive protein levels were low in a great majority of patients. Viral lower respiratory tract infection in children is often associated with bacterial-type upper respiratory tract infections. However, coexisting bacterial lower respiratory tract infections that induce systemic inflammatory response are seldom detected.
Output: Bacterial coinfections in children with viral wheezing
Background. Precision public health is a novel set of methods to target disease prevention and mitigation interventions to highrisk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods. Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso-and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results. Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions. Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.
Output: Clinical Infectious Diseases Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda
Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens. Front. Microbiol. 6:532. A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP) which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1) associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs) of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from five distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR), which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, two of Klebsiella pneumoniae and one of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100, 100%, respectively), H. influenzae (92.3, 97.9%, respectively), M. pneumoniae (69.2, 99.0%, respectively), K. pneumoniae (100, 100%, respectively), and M. catarrhalis (100, 100%, respectively). Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in nine of Staphylococcus spp. and one of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics.
Output: Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens
The current study was designed to assess the inhibitory activity of Broussonetia papyrifera-derived polyphenols against 3-chymotrypsin-like and papain-like coronavirus cysteine proteases. The isolated compounds were broussochalcone B (1), broussochalcone A (2), 4-hydroxyisolonchocarpin (3), papyriflavonol A (4), 3 0 -(3-methylbut-2-enyl)-3 0 ,4,7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), broussoflavan A (8), kazinol F (9), and kazinol J (10). All polyphenols were more potent against papain-like protease (PL pro ) than against 3-chymotripsin-like protease (3CL pro ); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PL pro with an IC 50 value of 3.7 lM. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PL pro were determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents. ARTICLE HISTORY
Output: Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors
ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.
Output: Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome
During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article in mBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1 ؉ ) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion.
Output: Chasing Ebola through the endosomal labyrinth
Coronavirus M proteins represent the major protein component of the viral envelope. They play an essential role during viral assembly by interacting with all of the other structural proteins. Coronaviruses bud into the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), but the mechanisms by which M proteins are transported from their site of synthesis, the ER, to the budding site remain poorly understood. M in the ER. The second motif, 199 KxGxYR 204 , was responsible for retaining the M protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage toward the plasma membrane. We further confirmed the role of 199 KxGxYR 204 as a TGN retention signal by using chimeras between MERS-CoV M and the M protein of infectious bronchitis virus (IBV). Our results indicated that the C-terminal domains of both proteins determine their specific localization, namely TGN and ERGIC/cis-Golgi for MERS-M and IBV-M, respectively. Our findings indicate that MERS-CoV M protein localizes to the TGN because of the combined presence of an ER export signal and a TGN retention motif.
Output: The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal
DNA and RNA modifications have important functions, including the regulation of gene expression. Existing methods based on short-read sequencing for the detection of modifications show difficulty in determining the modification patterns of single chromosomes or an entire transcript sequence. Furthermore, the kinds of modifications for which detection methods are available are very limited. The Nanopore sequencer is a single-molecule, long-read sequencer that can directly sequence RNA as well as DNA. Moreover, the Nanopore sequencer detects modifications on long DNA and RNA molecules. In this review, we mainly focus on base modification detection in the DNA and RNA of mammals using the Nanopore sequencer. We summarize current studies of modifications using the Nanopore sequencer, detection tools using statistical tests or machine learning, and applications of this technology, such as analyses of open chromatin, DNA replication, and RNA metabolism.
Output: Recent advances in the detection of base modifications using the Nanopore sequencer
Perinatal death (PD) is a devastating obstetric complication. Determination of cause of death helps in understanding why and how it occurs, and it is an indispensable aid to parents wanting to understand why their baby died and to determine the recurrence risk and management in subsequent pregnancy. Consequently, a perinatal death requires adequate diagnostic investigation. An important first step in the analysis of PD is to identify the case circumstances, including relevant details regarding maternal history, obstetric history and current pregnancy (complications are evaluated and recorded). In the next step, placental examination is suggested in all cases, together with molecular cytogenetic evaluation and fetal autopsy. Investigation for fetalematernal hemorrhage by Kleihauer is also recommended as standard. In cases where parents do not consent to autopsy, alternative approaches such as minimally invasive postmortem examination, postmortem magnetic resonance imaging, and fetal photographs are good alternatives. After all investigations have been performed it is important to combine findings from the clinical review and investigations together, to identify the most probable cause of death and counsel the parents regarding their loss.
Output: Perinatal death investigations: What is current practice?
Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA/AA: OR = 0.44, 95%CI, 0.23-0.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG/GA versus AA: OR = 1.86,95%CI, 1.01-3.45), superdominant (GA versus GG/AA: OR = 1.81,95%CI, 1.02-3.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA/AA: OR = 0.27,95%CI, 0.10-0.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.
Output: Different Associations between DC-SIGN Promoter-336G/A (rs4804803) Polymorphism with Severe Dengue in Asians and South-Central Americans: a Meta-Analysis
This paper surveys some of the important insights that molecular evolution has contributed to evolutionary medicine; they include phage therapy, cancer biology, helminth manipulation of the host immune system, quality control of gametes, and pathogen outbreaks. Molecular evolution has helped to revolutionize our understanding of cancer, of autoimmune disease, and of the origin, spread, and pathogenesis of emerging diseases, where it has suggested new therapies, illuminated mechanisms, and revealed historical processes: all have practical therapeutic implications. While much has been accomplished, much remains to be done. Phage therapy had short-lived success for a patient in Belgium who had acquired a P. aeruginosa infection after developing necrotic pressure sores during the extended hospitalization that followed bowel surgery (Jennes et al. 2017) .
Output: Frontiers in Molecular Evolutionary Medicine
Phenanthroquinolizidine alkaloids a b s t r a c t The stereoselective synthesis of epi-thieno analogues of the phenanthroquinolizidine bioactive alkaloids (À)-Cryptopleurine and (À)-(15R)-Hydroxycryptopleurine was achieved in five steps starting from easily available enantiopure (S)-2-aminoadipic acid used as chiral pool and nitrogen atom source. During these investigations, both p-cationic cyclization of chiral N-thienylmethyl-6-oxopipecolinic acids into pure (S)keto-lactams and theirs regioselective and diastereoselective reduction, considered as key steps of this sequence, were studied. Of particular interest, the FriedeleCrafts cyclization using (CF 3 CO) 2 O/BF 3 $Et 2 O show that near the expected keto-lactams, enamides and enamidones containing trifluoromethyl residue were isolated. A mechanism leading to the latter products with high synthetic potential was discussed.
Output: Use of chiral-pool approach into epi-thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids
A group of 4-month-old beef calves were examined for clinical respiratory disease with labored breathing, coughing, and fevers of over 104°F. Necropsy of one of the calves revealed lungs that were not collapsed but had red mottled appearance on cut surface. Assessment of lung tissue by bacterial culture and PCR did not reveal bovine bacterial or viral respiratory pathogens. Histopathology of affected tissues and lymph nodes revealed larval ascarid nematodes. In combination with phylogenetic analysis, amplification and sequencing of ITS1 was used to identify the larvae as Ascaris.
Output: Respiratory disease associated with migrating Ascaris larvae in a beef calf
Background: Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). Results: A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. Conclusions: Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.
Output: Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials
A series of 2-(2-chloroquinolin-3-yl)-5-((aryl)benzylidene)-3-(4-oxo-2-phenylquinazolin-3(4H)-yl)thiazolidin-4-ones (V) 1-12 have been synthesized. In order to establish optimization of different parameters of chemical transformation, that is the reaction pathway for each step and reaction conditions in the each step, in the present paper, different solvents and catalysts were used. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1 H NMR and 13 C NMR spectral data. All the newly synthesized compounds were screened against various strains of bacteria and fungi. ª 2011 King Saud University. Production and hosting by Elsevier B.V.
Output: Synthesis and antimicrobial activity of novel quinazolinone-thiazolidine-quinoline compounds
For the purpose of this work, insect biotechnology, which is also known as yellow biotechnology, is the use of insects as well as insect-derived cells or molecules in medical (red biotechnology), agricultural (green biotechnology), and industrial (white) biotechnology. It is based on the application of biotechnological techniques on insects or their cells to develop products or services for human use. Such products are then applied in agriculture, medicine, and industrial biotechnology. Insect biotechnology has proven to be a useful resource in diverse industries, especially for the production of industrial enzymes including chitinases and cellulases, pharmaceuticals, microbial insecticides, insect genes, and many other substances. Insect cells (ICs), and particularly lepidopteran cells, constitute a competitive strategy to mammalian cells for the manufacturing of biotechnology products. Among the wide range of methods and expression hosts available for the production of biotech products, ICs are ideal for the production of complex proteins requiring extensive posttranslational modifi cation. The progress so far made in insect biotechnology essentially derives from scientifi c breakthroughs in molecular biology, especially with the advances in techniques that allow genetic manipulation of organisms and cells. Insect biotechnology has grown tremendously in the last 30 years.
Output: Insect Biotechnology
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Vaccine 23 (2005) 3446-3452 rOv-ASP-1, a recombinant secreted protein of the helminth Onchocerca volvulus, is a potent adjuvant for inducing antibodies to ovalbumin, We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.
Output: HIV-1 polypeptide and SARS-CoV peptide antigens
Chemokines and their receptors function in the recruitment and activation of cells of the immune system to sites of inflammation. As such, chemokines play an important role in mediating pathophysiological events during microbial infection. In particular, CXCL9, 10 and 11 and their cognate receptor CXCR3 have been associated with the clinical course of several infectious diseases, including severe acute respiratory syndrome (SARS) and influenza. While CXCL9, 10 and 11 share the same receptor and have overlapping functions, each can also have unique activity in host defense. The lack of a preferred characterized animal model for SARS has brought our attention to ferrets, which have been used for years in influenza studies. The lack of immunological reagents for ferrets prompted us to clone CXCL9, 10, 11 and CXCR3 and, in the case of CXCL10, to express the gene as a recombinant protein. In this study we demonstrate that endogenous ferret CXCL10 exhibits similar mRNA expression patterns in the lungs of deceased SARS patients and ferrets experimentally infected with SARS coronavirus. This study therefore represents an important step towards development of the ferret as a model for the role of CXCL9, 10 and 11:CXCR3 axis in severe viral infections.
Output: Cloning, expression and characterization of ferret CXCL10 HHS Public Access
A quantitative PCR method was established to quantify human bocavirus (HBoV) genomic copies in clinical specimens from children with lower respiratory tract infections (LRTI) in China. A total of 257 respiratory tract specimens were tested, and 7 (2.7%) of these (all sputum samples) were positive, with genomic copies that ranged from 8.0 × 10 3 to 8.0 × 10 9 in the samples. The main clinical symptom of patients who were positive for HBoV DNA was a pneumonia-like syndrome represented by high fever and cough. Our results suggest that HBoV may be an important etiological agent of LRTI in children in China. Finding
Output: Quantification of human bocavirus in lower respiratory tract infections in China
Background: Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans. HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various diagnostic, immunization and pathogenesis studies. Plants are considered as an expression system for producing safe and inexpensive biopharmaceutical proteins. Although invention of transgenic (stable) tobacco plants expressing HCVcp with proper antigenic properties was recently reported, no data for "transient-expression" that is currently the method of choice for rapid, simple and lower-priced protein expression in plants is available for HCVcp. Objectives: The purpose of this study was to design a highly codon-optimized HCVcp gene for construction of an efficient transient-plant expression system for production of HCVcp with proper antigenic properties in a regional tobacco plant (Iranian Jafarabadi-cultivar) by evaluation of different classes of vectors and suppression of gene-silencing in tobacco. A codon-optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL peptide in tandem (from N-to C-terminal) was designed and inserted into potato virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions. The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens and vacuum infiltrated into tobacco leaves. The effect of gene silencing suppressor P19 protein derived from tomato bushy stunt virus on the expression yield of HCVcp by each construct was also evaluated by co-infiltration in separate groups. The expressed HCVcp was evaluated by dot and western blotting and ELISA assays. Results: The codon-optimized gene had an increased adaptation index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in tobacco and removed the possible deleterious effect of "GGTAAG" splice site in native HCVcp. Blotting assays via specific antibodies confirmed the expression of the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19 co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for diagnostic/immunization applications. Conclusions: By employment of gene optimization strategies, use of viral-based vectors and suppression of plant-derived gene silencing effect, efficient transient expression of HCVcp in tobacco with proper antigenic properties could be possible.
Output: Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications
Background: Respiratory viral infections are a major cause of hospitalisation in infants <1 year and might cause severe symptoms in preterm infants. Our aim was to analyse admissions due to respiratory infections in moderate, late and term infants, and to identify risk factors for hospitalisation in preterm versus term. Methods: Prospective study in a cohort of moderate and late preterm, and term infants born between October/2011 and December/2012. Admissions due to respiratory infections during the first year of life were analysed and compared among moderate (32---33), late (34---36) and term infants. Sixteen respiratory viruses were detected by RT-PCR. Clinical data were collected. Results: 30 (20.9%) out of 143 preterm infants required admission for respiratory infection, versus 129 (6.9%) of 1858 term infants born in the same period (p < 0.0001, OR: 3.6 CI 2.0 to 5.0). Hospitalised children had a higher prevalence of hyaline membrane disease (HMD) at birth (p < 0.001, OR: 7.7 CI: 2.121 to 27.954) and needed more mechanical ventilation (p < 0.001, OR: 5.7 CI: 1.813 to 18.396). Virus was identified in 25/30 (83%) preterm babies, and in 110/129 (85%) term infants. The most frequent viruses in preterm infants were RSV (76%) rhinovirus (20%). Clinical and epidemiological characteristics among term and preterm infants were similar. Conclusions: The risk of respiratory admissions during the first year of life is up to 3.6 times higher in moderate and late preterm. Once admitted, clinical features of respiratory episodes requiring hospitalisation are similar among term and preterm infants. Hyaline membrane disease and mechanical ventilation were also risk factors for respiratory admissions.
Output: Allergologia et immunopathologia Hospital admission due to respiratory viral infections in moderate preterm, late preterm and term infants during their first year of life
Nowadays, stock market is becoming a popular investment platform for both institutional and individual investors. The current financial information systems serve to provide latest information. However, they lack sophisticated analytical tools. This paper proposes a new architecture for financial information systems. The developed prototype is entitled as the Multi-level and Interactive Stock Market Investment System (MISMIS). It is specially designed for investors to build their financial models to forecast stock price and index. The performance of the financial models can be evaluated on a virtual trading platform. There are other features in MISMIS that are tailor-made to handle financial data; these include synchronized time frame, time series prediction techniques, preprocessing and transformation functions, multi-level modeling and interactive user interface. To illustrate the capability of MISMIS, we have evaluated strategies of trading the future options of Hang Seng Index (HSI). We find that historical HSI, Dow Jones Index, property price index, retailing sales figure, prime lending rate, and consumer price index in Hong Kong are essential factors affecting the performance of the trading of HSI's future option. Also there are some feedbacks from the in-depth interviews of six financial consultant upon how they perceived the prototype MISMIS.
Output: MISMIS -A comprehensive decision support system for stock market investment Keywords: Stock market intelligent trading system Decision support system Time series analysis Hang Seng index Multi-level system
Coronaviruses (CoVs) infect humans and many animal species, and are associated with respiratory, enteric, hepatic, and central nervous system diseases. The large size of the CoV genome and the instability of some CoV replicase gene sequences during its propagation in bacteria, represent serious obstacles for the development of reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these limitations, several alternatives to more conventional plasmid-based approaches have been established in the last thirteen years. In this report, we briefly review and discuss the different reverse genetic systems developed for CoVs, paying special attention to the severe acute respiratory syndrome CoV (SARS-CoV).
Output: CORONAVIRUS REVERSE GENETIC SYSTEMS: INFECTIOUS CLONES AND REPLICONS
Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses. Citation: Lasecka L, Baron MD (2014) The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space. PLoS ONE 9(4): e94656.
Output: The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space
Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.
Output: Targeted Strategies for Henipavirus Therapeutics
All cases were confirmed by real-time RT-PCR or chest computer tomography (CT). The survivors were followed up until March 4,2020. Clinical data, including demographic characteristic, presentation, underlying illness, exposure history, laboratory examination, radiology and prognosis were enrolled and analyzed by SPSS 19.0 software. Results There were 197 adult discharged patients with COVID-19 in this study. Statistical analysis indicated that the average age was 55.94 years, and female patients were 99(50.3%).Those patients mainly resided in urban with exposure history in 2 weeks, while 7 medical staffs were infected. Fever (77.6%%), cough (43.6%) and weakness (14.7%) were the common symptoms. Leukocytes were mainly normal or decreased in 185 patients (92.9%), both lymphocytes and eosinophils were below normal range, the ratios were 56.9% and 50.3%, respectively. On the contrary, lactate dehydrogenases raised in 65 patients. C-reactive protein (72.4%) elevated in the most of patients. The sensitivity of RT-PCR was 63.5%. Chest CT indicated that bilateral patchy shadows (69.0%) were the most common imaging manifestations.169(85.8%) patients recovered and transferred to a designated hospital for observation, and the others (14.2%) turned worst and died of acute respiratory failure. Conclusion COVID-19 infection with highly contagious have become a life-threaten public healthy problem, the sensitivity of RT-PCR was limited. Chest CT scan was recommended for the suspected patients. Furthermore, lymphocytopenia and eosinophils declining without leukocytes increasing may be considered as a useful evidence for the diagnosis.
Output: Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang, Hubei
medRxiv preprint Interpretation Parameters that successfully reproduce the observed number of cases indicate that both R 0 and the prevalence of the virus might be underestimated. This is in concordance with the newest research on undocumented COVID-19 cases. Consequently, the actual mortality rate is putatively lower than estimated. Confirmation of the pandemic characteristic by further refinement of the model and screening tests is crucial for developing an effective strategy for the global epidemiological crisis. 1 Balcan D, Gonçalves B, Hu H, Ramasco JJ, Colizza V, Vespignani A. Modeling the spatial spread of infectious diseases: the GLobal Epidemic and Mobility computational model. J Comput Sci 2010; 1 : 132-45. 2 Van den Broeck W, Gioannini C, Gonçalves B, Quaggiotto M, Colizza V, Vespignani A. The GLEaMviz computational tool, a publicly available software to explore realistic epidemic spreading scenarios at the global scale. BMC Infect Dis 2011; 11 : 37. 3 Tizzoni M, Bajardi P, Poletto C, et al. Real-time numerical forecast of global epidemic spreading: case study of 2009 A/H1N1pdm. BMC Med 2012;
Output: From a single host to global spread. The global mobility based modelling of the COVID-19 pandemic implies higher infection and lower detection rates than current estimates
The major biochemical and thermodynamic features of nucelocapsid protein of SARS coronavirus (SARS _ NP) were characterized by use of non-denatured gel electrophoresis, size-exclusion chromatographic and surface plasmon resonance (SPR) techniques. The results showed that SARS _ NP existed in vitro as oligomer, more probably dimer, as the basic functional unit. This protein shows its maximum conformational stability near pH 9.0, and it seems that its oligomer dissociation and protein unfolding occur simultaneously. Thermal-induced unfolding for SARS _ NP was totally irreversible. Both the thermal and chemical denaturant-induced denaturation analyses showed that oligomeric SARS _ NP unfolds and refolds through a two-state model, and the electrostatic interactions among the charge groups of SARS _ NP made a significant contribution to its conformational stability. D Abbreviations: SARS _ CoV, severe acute respiratory syndrome coronavirus; SARS _ NP, nucleocapsid protein of SARS; SPR, surface plasmon resonance; GuHCl, guanidine hydrochloride; CD, circular dichroism; T m and C m , transition midpoints of thermal and chemical denaturations; IPTG, isopropyl-h-d-thiogalasctopyranoside; N and U, native and unfolded states.
Output: In vitro biochemical and thermodynamic characterization of nucleocapsid protein of SARS
Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (60.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.
Output: How Long Will My Mouse Live? Machine Learning Approaches for Prediction of Mouse Life Span
Introduction: The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. Methods: This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). Results: Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. Conclusion: Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.
Output: Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study