niryuu/sni-each-converted huggingface dataset:
We consider a three-stage game where a public firm and a private firm choose R&D, location, and price, under the assumption that R&D spillovers rely on their locations. We show that, in equilibrium, whether the public firm engages in innovation more aggressively than the private firm depends on the degree of spillovers. Moreover, firms' equilibrium locations exhibit neither maximal nor minimal differentiation. Finally, privatization could reduce social welfare because it may generate inefficient location and insufficient R&D investment. This suggests that a mixed duopoly could be socially preferable to a private duopoly in the presence of endogenous R&D spillovers. JEL Classification O30 · H42 · L13 · R32
Output: Endogenous R&D spillover and location choice in a mixed oligopoly
Severe acute respiratory syndrome (SARS), caused by the novel coronavirus SARS-CoV, produced a scare Abstract when it appeared in 2003 in China and later quickly spread to other countries around the world. Although it has since disappeared, its threat to human health remains. Therefore, studies on the prevention and treatment of SARS are important for dealing with epidemics of this and other infectious diseases. The most promising newly developed technology for intervention in SARS may be RNA interference, an endogenous cellular process for the inhibition of gene expression mediated by sequence-specific double-stranded RNAs. Numerous studies have reported the therapeutic potential of RNA interference for the treatment of various human diseases ranging from cancers to infectious diseases such as HIV and hepatitis. To date, most studies on inhibition of SARS-CoV replication using small interfering RNAs (siRNAs) have been conducted in cell lines in vitro. One study using siRNAs to inhibit SARS-CoV infection in Rhesus macaques demonstrated that siRNAs were effective both prophylactically and therapeutically with no adverse effects in the animals. Challenges remaining for the application of siRNA in vivo for SARS prevention and treatment include the specificity of the siRNAs and the efficiency of delivery. However, with improvements in siRNA design and delivery methods, RNA interference has the potential to become another major weapon for combating dangerous infections due to viruses such as SARS-CoV.
Output: Therapeutic and Prophylactic Potential of Small Interfering RNAs against Severe Acute Respiratory Syndrome Progress to Date
XendoU is the first endoribonuclease described in higher eukaryotes as being involved in the endonucleolytic processing of intron-encoded small nucleolar RNAs. It is conserved among eukaryotes and its viral homologue is essential in SARS replication and transcription. The large-scale purification and crystallization of recombinant XendoU are reported. The tendency of the recombinant enzyme to aggregate could be reversed upon the addition of chelating agents (EDTA, imidazole): aggregation is a potential drawback when purifying and crystallizing His-tagged proteins, which are widely used, especially in highthroughput structural studies. Purified monodisperse XendoU crystallized in two different space groups: trigonal P3 1 21, diffracting to low resolution, and monoclinic C2, diffracting to higher resolution.
Output: Structural Biology and Crystallization Communications Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins
1. Data collection. Epidemiological data were collected from a variety of online sources. If we were able to find reports listing numbers of confirmed and suspected cases, we used that information. If the epidemiological curve was available online as a graph, which is the case for data obtained from the CDC (Centers for Disease Control and Prevention) and Eurosurveillance sites, we estimated numbers from the graph and matched the plot of the estimated data with the online source. This can conveniently be done in Excel by plotting our estimated numbers on a graph with a transparent background and superimposing the resulting plot on a copy of the epidemiological curve posted online. The data we used are available online at github.com/ JocelineLega/EpiGro. • Data for the 2014-15 chikungunya outbreak in the PAHO countries and territories were extracted from weekly reports published on the PAHO website (1), for the 71-week period from January 3, 2014 to May 8, 2015. Confirmed (autochthonous + imported) and suspected cases are included in this analysis. Not all countries provided weekly revisions of the total number of reported cases, leading to groups of consecutive data points with equal value. In the calculation of the outbreak growth rate, we use a time unit of one week. We do not compensate for the fact that the 53 rd week of 2014 has only 4 days; since the data are first smoothed and then interpolated, such a variation leads to a change in the instantaneous growth rate that is comparable to the size of uncertainties due to fluctuations in the number of reported cases, and is therefore negligible. Excel files with these data are provided for the Dominican Republic (CHIK Dom Rep.xlsx), Guadeloupe (CHIK Guadeloupe.xlsx), and Dominica (CHIK Dominica.xlsx).
Output: DATA-DRIVEN OUTBREAK FORECASTING WITH A SIMPLE NONLINEAR GROWTH MODEL TECHNICAL APPENDICES
We review behavioural change models (BCMs) for infectious disease transmission in humans. Following the Cochrane collaboration guidelines and the PRISMA statement, our systematic search and selection yielded 178 papers covering the period 2010-2015. We observe an increasing trend in published BCMs, frequently coupled to (re)emergence events, and propose a categorization by distinguishing how information translates into preventive actions. Behaviour is usually captured by introducing information as a dynamic parameter (76/178) or by introducing an economic objective function, either with (26/178) or without (37/178) imitation. Approaches using information thresholds (29/178) and exogenous behaviour formation (16/178) are also popular. We further classify according to disease, prevention measure, transmission model (with 81/178 population, 6/178 metapopulation and 91/178 individuallevel models) and the way prevention impacts transmission. We highlight the minority (15%) of studies that use any real-life data for parametrization or validation and note that BCMs increasingly use social media data and generally incorporate multiple sources of information (16/178), multiple types of information (17/178) or both (9/178). We conclude that individual-level models are increasingly used and useful to model behaviour changes. Despite recent advancements, we remain concerned that most models are purely theoretical and lack representative data and a validation process.
Output: Behavioural change models for infectious disease transmission: a systematic review (2010-2015)
Ebolavirus, a member of the Filoviridae family of negative-sense RNA viruses, causes severe haemorrhagic fever leading up to 90% lethality. Ebolavirus matrix protein VP40 is involved in the virus assembly and budding process. The RNA binding pocket of VP40 is considered as the drug target site for structure based drug design. High Throughput Virtual Screening and molecular docking studies were employed to find the suitable inhibitors against VP40. Ten compounds showing good glide score and glide energy as well as interaction with specific amino acid residues were short listed as drug leads. These small molecule inhibitors could be potent inhibitors for VP40 matrix protein by blocking virus assembly and budding process. ISSN 0973-2063 (online) 0973-8894 (print) Bioinformation 9(6): 286-292 (2013) 287 © 2013 Biomedical Informatics replication [23]. C-terminal domain of VP40 is required for membrane association [24, 25]. open access ISSN 0973-2063 (online) 0973-8894 (print) Bioinformation 9(6): 286-292 (2013) 289
Output: Hypothesis High-throughput virtual screening and docking studies of matrix protein vp40 of ebola virus
Seven fragments of the spike (S) gene cDNA of transmissible gastroenteritis virus (TGEV), as well as the full length cDNA, were cloned and expressed in baculovirus vectors. Piglets were immunized with cells infected with the recombinant viruses. Each of the recombinants induced TGEV-specific antibodies detected in a fixed cell enzyme immunoassay. The amino terminal half of the S protein, containing all four major antigenic sites (A, B, C and D), and encoded by a 2.2 kb fragment of the S gene, induced virus neutralizing (VN) antibody titers comparable with those induced by the complete S protein. Recombinant proteins lacking the A antigenic site, or with a deletion including the putative receptor binding sites and the D antigenic site, were not capable of inducing levels of VN antibodies similar to those induced by the whole S protein.
Output: Immunogenicity of the S protein of transmissible gastroenteritis virus expressed in baculovirus
Background: Infectious bronchitis is highly contagious and constitutes one of the most common and difficult poultry diseases to control. IBV is endemic in probably all countries that raise chickens. It exists as dozens of serotypes/genotypes. Only a few amino acid differences in the S1 protein of vaccine and challenge strains of IBV may result in poor protection. Tropism of IBV includes the respiratory tract tissues, proventriculus and caecal tonsils of the alimentary tract, the oviduct and the kidney. Results: Infectious bronchitis virus (IBV) strain closely related to Massachusetts (Mass) serotype was isolated from broiler chickens suffering from severe renal and respiratory distresses. The isolate was serologically identified by Dot-ELISA and further characterized by RT-PCR then genotyped using S1 gene sequence analysis. Alignment of the S1 sequence of the isolate with 16 IBV strains revealed high homology to isolates related to Mass serotype. Inoculation with the strain reproduced the disease in experimental 1-day-old chickens and resulted in 20% mortality, severe renal and moderate respiratory distresses. Marked histopathological changes in both kidney and trachea were observed in experimentally infected chickens. A protection study using the H120 live attenuated vaccine showed low protection rate in spite of high S1 sequence homology (97%). Protection based criteria were: virus re-isolation attempts from trachea, tracheal and renal histopathology as well as IBV antigens detection by immunofluorescent antibody technique in kidney sections. Conclusion: Periodical evaluation of cross-protective capabilities of IBV vaccine(s) versus recently recovered field isolates should be performed to ensure optimum control of IBV.
Output: Virology Journal S1 gene sequence analysis of a nephropathogenic strain of avian infectious bronchitis virus in Egypt
Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)-poly(ethylene glycol) (PEI-PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism. In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13 (APN/CD13) and caveolin 1 (CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment, TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin (MβCD), further identifying the involvement of caveolae-mediated endocytosis (CvME). This conclusion was also verified by endocytosis inhibitor experiments.
Output: A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified multifunctional nanoparticles and vascular epithelial cells-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Background: The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases. Methods: Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases. Their clinicopathological characteristics were reviewed and analyzed. Cultures for mycobacteria were performed. The indirect proportion method with Löwenstein-Jensen (L-J) medium was used for first-line drug susceptibility test. T-SPOT.TB assay was performed according to the manufacturer's instructions. Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables). The χ 2 test was used for comparisons between proportions. Results: The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male. 16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical difference in the positivity rate between them (P < 0.01). Conclusions: In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China. Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination. In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.
Output: The performance of interferon-gamma release assay in nontuberculous mycobacterial diseases: a retrospective study in China
Viral disease caused by the Yellow head virus (YHV) had great impact on economic loss in the aquaculture industry. Prevention or curing YHV disease is still not possible due to the lack of understanding of the basic mechanisms of YHV infection. In this report, the endocytosis inhibitors (chlorpromazine (CPZ), amiloride and methyl-β-cyclodextrin (MβCD)) were used to identify the cellular entry pathway of YHV. Pretreating shrimp with CPZ but not amiloride or MβCD followed by YHV challenge resulted in a significant reduction of YHV levels, suggesting that YHV entered the shrimp cells via clathrin-mediated endocytosis. Next, the major component of the clathrin-coated vesicle, Penaeus monodon clathrin heavy chain (PmCHC) was cloned and characterized. The complete coding sequence of PmCHC is 5055 bp encoding a putative protein of 1684 amino acids. Specific silencing of PmCHC mRNA by dsRNA-PmCHC showed an inhibition of YHV replication for 48 h post YHV injection as well as exhibiting a delay in shrimp mortality. These results indicated that PmCHC was an essential component for YHV infection of shrimp cells.
Output: Successful yellow head virus infection of Penaeus monodon requires clathrin heavy chain
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3-and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1 −/− ) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virusinduced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.
Output: Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations
Background-The potential risks associated with "toilet plume" aerosols produced by flush toilets is a subject of continuing study. This review examines the evidence regarding toilet plume bioaerosol generation and infectious disease transmission. Methods-The peer-reviewed scientific literature was searched to identify articles related to aerosol production during toilet flushing, as well as epidemiologic studies examining the potential role of toilets in infectious disease outbreaks. Results-The studies demonstrate that potentially infectious aerosols may be produced in substantial quantities during flushing. Aerosolization can continue through multiple flushes to expose subsequent toilet users. Some of the aerosols desiccate to become droplet nuclei and remain adrift in the air currents. However, no studies have yet clearly demonstrated or refuted toilet plume-related disease transmission, and the significance of the risk remains largely uncharacterized. Conclusion-Research suggests that toilet plume could play a contributory role in the transmission of infectious diseases. Additional research in multiple areas is warranted to assess the risks posed by toilet plume, especially within health care facilities. An association between inhalable bioaerosols produced from disturbed sewage and the transmission of infectious disease has been proposed for over 100 years. However, little study has been devoted to characterizing the potential risks posed by the "toilet plume" Gerba et al 10 seeded a siphonic gravity-flow toilet with Escherichia coli and sequentially placed 3 arrays of settle plates on the floor around the toilet, with each set exposed for 2 Johnson et al.
Output: Lifting the lid on toilet plume aerosol: A literature review with suggestions for future research
Bats are the natural host reservoir for range of emerging and re-emerging viruses, many of which cause significant morbidity and mortality in other mammals, yet appear to result in no clinical consequences for bats. The ability of bats to coexist with a variety of viruses presents an interesting immunological problem that has not been examined in any detail but which could provide significant insights into the evolution of antiviral mechanisms in mammals. Towards a better understanding of the bat immune system, we analysed the expressed heavy chain variable (VH) regions of antibodies from the black flying fox, Pteropus alecto. The germline repertoire of the closely related Pteropid bat, Pteropus vampyrus, whose genome has been sequenced was also examined for comparative purposes. Representative VH genes were found in all three mammalian VH clans (I, II and III) in both the expressed P. alecto VH repertoire and the germline P. vampyrus VH repertoire. Evidence for the use of multiple heavy chain diversity (DH) and joining (JH) segments for the generation of diverse VDJ rearrangements was also present in the expressed antibody repertoire of P. alecto. The long period of co-evolutionary history of bats with viruses may have resulted in a variety of highly specific VH segments being hardwired into the genomes of bats and may have implications for their ability to successfully cope with a diversity of viral antigens.
Output: Immunoglobulin heavy chain diversity in Pteropid bats: evidence for a diverse and highly specific antigen binding repertoire
Feline infectious peritonitis (FIP) is a fatal disease in cats worldwide. The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results. RNA was extracted from body cavity effusion samples of 71 cats, including 34 samples from cats with a definitive diagnosis of FIP, and 37 samples of control cats with similar clinical signs but other confirmed diseases. Two reaction mixtures (Isothermal Mastermix, OptiGene Ltd.and PCRun™ Molecular Detection Mix, Biogal) were tested using the same primers, which were designed to bind to a conserved region of the FCoV membrane protein gene. Both assays were conducted under isothermal conditions (61°C-62°C). Using the Isothermal Mastermix of OptiGene Ltd., amplification times ranged from 4 and 39 min with a sensitivity of 35.3% and a specificity of 94.6% for the reported sample group. Using the PCRun™ Molecular Detection Mix of Biogal, amplification times ranged from 18 to 77 min with a sensitivity of 58.8% and a specificity of 97.3%. Although the RT-LAMP assay is less sensitive than real time reverse transcription PCR (RT-PCR), it can be performed without the need of expensive equipment and with less hands-on time. Further modifications of primers might lead to a suitable in-house test and accelerate the diagnosis of FIP.
Output: Detection of feline Coronavirus in effusions of cats with and without feline infectious peritonitis using loop-mediated isothermal amplification
Each problem that I solved became a rule, which served afterwards to solve other problems." -Rene Descartes the management of large-scale chemical, biological, radiological, nuclear, and explosives (CBRNE) events with mass casualties. These projects are funded by Defence Research and Development Canada, an agency within the Federal Department of National Defence, within its CBRNE Research and Technology Initiative (CRTI) preparing Canada's CBRNE response capabilities. Each project involves numerous public and private civilian partners as well as university partners, which is the category to which our team belongs. We are subcontracted by an industry client in charge of developing the software. When an adverse event escalates into a criminal investigation, it becomes very difficult to control and combine information into a manageable format. Numerous professionals representing different responder agencies, public health authorities, and others are involved, or become involved as the magnitude of an adverse event with mass casualties unfolds. In such events, chaos and uncertainty prevail; things happen very quickly, well before the first responders arrive on the scene, and last until a clearer picture of the nature and scope of the event can be formed, a command post has been set up, and a responsible action plan can be formulated and executed. The combined role of the first-responder teams is to preserve life, property, and equipment, while preventing the damage from spreading, providing triage to casualties on Usability in Government Systems.
Output: Emergency Response in Simulated Terrorist Attacks: Usability Lessons Learned 7
Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence. They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the "birth") of a completely new protein from a second frame. In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation. This results in erroneous interpretation of mutational studies and in a significant waste of resources. Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes. Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases. We thus assembled a highquality dataset of 80 viral overlapping genes whose expression is experimentally proven. Many of them were not present in databases. We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition. In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes. Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function. Six proven mammalian overlapping genes also followed this bias. We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them.
Output: Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes
The recent spread of next-generation sequencing techniques has facilitated transcriptome analyses of non-model plants. As a result, many of the genes encoding enzymes related to the production of specialized metabolites have been identified. Compounds derived from 2,3-oxidosqualene (the common precursor of sterols, steroids and triterpenoids), a linear compound of 30 carbon atoms produced through the mevalonate pathway, are called triterpenes. These include essential sterols, which are structural components of biomembranes; steroids such as the plant hormones, brassinolides and the toxin in potatoes, solanine; as well as the structurally diverse triterpenoids. Triterpenoids containing one or more sugar moieties attached to triterpenoid aglycones are called triterpenoid saponins. Triterpenoid saponins have been shown to have various medicinal properties, such as anti-inflammatory, anticancerogenic and antiviral effects. This review summarizes the recent progress in gene discovery and elucidates the biochemical functions of biosynthetic enzymes in triterpenoid saponin biosynthesis. Special focus is placed on key players in generating the structural diversity of triterpenoid saponins, cytochrome P450 monooxygenases (P450s) and the UDPdependent glycosyltransferases (UGTs). Perspectives on further gene discovery and the use of biosynthetic genes for the microbial production of plant-derived triterpenoid saponins are also discussed.
Output: P450s and UGTs: Key Players in the Structural Diversity of Triterpenoid Saponins
Background: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Methods: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. Results: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8 + T cell response. Conclusions: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.
Output: Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice
A prospective stud)! was carried out to determine the epidemiology and etiology of acute gastroenteritis on the general infant ward oj The Montreal Children's Hospital in the late fall of /976. Diarrhea occurred in 4/ of /65 infants (25%), with probable nosocomial acquisition in 26 patients. Two infants each had two episodes of diarrhea. and one had three. A putative pathogen was found In 3/ of 45 case episodes (69%). Virus-like particles were present in 28 o] 45 patients, and in 24 of 74 asymptomatic room contacts. Particles belonging to six morphologic classes were identified: adenovirus. rota virus, minirotavlrus, calicivirus, plcorna-parvovirus, and coronavirus. More than one agent was identified in /2 infants with diarrhea and in five asymptomatic room contacts. No wardwide etiologic pal/ern was evident, but minirotavirus or caltcivirus or both were associated with diarrhea in 10 patients, accompanied by vomiting in /5 of these infants. Moreover, spread oj individual agents was almost entirely limited to minirotavirus and calicivirus, with diarrhea in six of ten. and four of seven, virus positive room contacts. respectively. These viruses were also identified in stools from 12 infants without diarrhea, seven oJ whom had repeated vomiting. Data support the etiologic role oj mlnirotavirus and calicivirus in diarrhea or vomiting or both in hospitalized infants.
Output: Nosocomial infantile gastroenteritis associated with minirotavirus and calicivirus
Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response. Methods: In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface. Results: We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from MS patients and healthy donors upon Resiquimod-stimulation are enriched in a subpopulation of pDCs, characterized by a high amount of costimulatory molecules. Conclusion: Overall, these results indicate that activation of pDCs is enhanced in MS, likely due to a latent viral infection, and that costimulatory molecules expressed on pDCs could mediate a protective response against the viral trigger of autoimmunity.
Output: Molecular Sciences Communication Resiquimod-Mediated Activation of Plasmacytoid Dendritic Cells Is Amplified in Multiple Sclerosis
Objective: Health literacy has become a global issue, and it is important that patients and individuals are able to use information technology to access health information and educational services. The research objective is to develop a Saudi e-health literacy scale (SeHL) for measuring e-health literacy among Saudis suffering from non-communicable diseases (NCD). Methods: Overall, 14 relevant papers in related interdisciplinary fields were reviewed to select the most useful literacy dimensions. From these articles, we extracted the most common dimensions used to measure e-health literacy across the disciplines. Multiple workshops with multidisciplinary team members reviewed and evaluated items for SeHL. Results: Four key aspects of e-health literacy-use of technology/media, information-seeking, usefulness and confidence-were identified and integrated as e-health literacy dimensions. These will be used to measure e-health literacy among Saudi patients with NCDs. A translation from Arabic to English was performed in order to ensure that translation process was accurate. A SeHL scale was developed to measure e-health literacy among Saudi patients. By understanding e-health literacy levels, we will be able to create a patient-education system to be used by patients in Saudi Arabia. Conclusions: As information technology is increasingly used by people of all ages all over the world, e-health literacy has been identified as a key factor in determining health outcomes. To date, no comprehensive scale exists to assess e-health literacy levels among speakers of Arabic, particularly among people with NCD such as diabetes, cardiovascular diseases and hypertension.
Output: Saudi Arabia, 5 Prince Sultan Military Medical City, AlSulimaniah, Riyadh 11159, Saudi Arabia, 6 King Faisal Specialist and Research Center
Mouse hepatitis virus 3 (MHV 3) is either avirulent (resistant mice), hepatotropic (susceptible mice), or neurotropic (semisusceptible mice), depending on the strain of mice infected. In semisusceptible mice, infection led first to a transient meningitis, ependymitis, and leukoencephalitis, followed by a permanent communicating hydrocephalus and, later on, to a chronic thrombotic vasculitis affecting meningeal and parenchymal vessels at the brain stem level. Small foci of ischemic necrosis related to vascular occlusions were seen in the dorsal brain stem. Cyclophosphamide treatment of semisusceptible mice significantly reduced the meningeal infiltrates but did not prevent the development of hydrocephalus and other neuropathologic changes. Identical lesions occurred in fully susceptible mice infected with a low dose of virus, but no neurologic disorder could be induced in genetically resistant mice even following immunosuppression or intracranial inoculation. The leukoencephalitis differed from the demyelinating lesions observed with MHV 4. Vascular lesions were of particular interest. More attention should be given to the possibility of virus induced chronic cerebral vasculitis in man.
Output: Ependymitis, Leukoencephalitis, Hydrocephalus, and Thrombotic Vasculitis Following Chronic Infection by Mouse Hepatitis Virus 3 (MHV 3)*
Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu-and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems. DPP4 is a type II integral transmembrane glycoprotein expressed on many cell types, but appears also in soluble form in body fluids including cerebrospinal fluid 1 . As a serine protease, DPP4 cleaves dipeptides from oligopeptides and proteins containing proline/alanine in the penultimate position. DPP4 processes neuropeptides, hormones, cytokines and chemokines leading to their biological activation or inactivation. Potential substrates include incretins (glucagon-like peptide-1 and -2, and glucose-dependent insulinotropic polypeptide), bradykinin, Substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and tumour necrosis factor (TNF-α) 2-4 . In addition to the enzymatic activity, DPP4 has binding sites for adenosine deaminase (ADA) 5 Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RePoRts | (2018) 8:3490 |
Output: Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain OPEN
The SARS coronavirus main peptidase (SARS-CoV M pro ) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-SARS agents. Here, we report the crystal structure of M pro at a resolution of 1.82 Å, in space group P2 1 at pH 6.0. In contrast to the previously reported structure of M pro in the same space group at the same pH, the active sites and the S1 specificity pockets of both protomers in the structure of M pro reported here are in the catalytically competent conformation, suggesting their conformational flexibility. We report two crystal structures of M pro having an additional Ala at the N terminus of each protomer (M +A(-1) pro ), both at a resolution of 2.00 Å, in space group P4 3 2 1 2: one unbound and one bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the active sites and the S1 specificity pockets of both protomers of M +A(-1) pro are observed in a collapsed (catalytically incompetent) conformation; whereas they are in an open (catalytically competent) conformation in the APE-bound form. The observed conformational flexibility of the active sites and the S1 specificity pockets suggests that these parts of M pro exist in dynamic equilibrium. The structural data further suggest that the binding of APE to M pro follows an induced-fit model. The substrate likely also binds in an induced-fit manner in a process that may help drive the catalytic cycle.
Output: Crystal Structures Reveal an Induced-fit Binding of a Substrate-like Aza-peptide Epoxide to SARS Coronavirus Main Peptidase
This work describes and applies a methodology for estimating the impact of recirculating heating, ventilating, and air-conditioning (HVAC) particle filters on the control of size-resolved infectious aerosols in indoor environments using a modified version of the Wells-Riley model for predicting risks of infectious disease transmission. Estimates of risk reductions and associated operational costs of both HVAC filtration and equivalent outdoor air ventilation are modeled and compared using a case study of airborne transmission of influenza in a hypothetical office space. Overall, recirculating HVAC filtration was predicted to achieve risk reductions at lower costs of operation than equivalent levels of outdoor air ventilation, particularly for MERV 13e16 filters. Medium efficiency filtration products (MERV 7e11) are also inexpensive to operate but appear less effective in reducing infectious disease risks.
Output: HVAC filtration for controlling infectious airborne disease transmission in indoor environments: Predicting risk reductions and operational costs
Motivated by the rapid spread of COVID-19 all across the globe, we have performed simulations of a system dynamic epidemic spread model in different possible situations. The simulation, not only captures the model dynamic of the spread of the virus, but also, takes care of population and mobility data. The model is calibrated based on epidemic data and events specifically of Sultanate of Oman, which can easily be generalized. The simulation results are quite disturbing, indicating that, during a process of stringent social distancing and testing strategies, a small perturbation can lead to quite undesirable outcomes. The simulation results, although consistent in expected outcomes across changing parameters' values, also indicate a substantial mismatch with real numbers. An analysis of what can be the reason of this mismatch is also performed. Within these contradictions, for Oman, regarding the eradication of epidemic, the future is not extremely alarming.
Output: COVID-19 Outbreak in Oman: Model-Driven Impact Analysis and Challenges
Background: To increase understanding of human bacterial and parasitic pathogens in bats, we investigated the prevalence of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii in bats from China. Methods: Bats were captured from Mengyin County, Shandong Province of China using nets. DNA was extracted from the blood and spleen of bats for molecular detection of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii with specific primers for each species. Results: A total of 146 spleen samples and 107 blood samples of insectivorous bats, which belonged to 6 species within two families, were collected from Mengyin County, Shandong Province of China. We found that two Eptesicus serotinus (2/15, 13.3%) were positive for Babesia vesperuginis. We were unable to detect genomic sequences for Rickettsia spp., Anaplasma spp. and Coxiella burnetii. Conclusions: To our knowledge, our study showed for the first time the presence of Babesia vesperuginis in Eptesicus serotinus collected from China, suggesting that Babesia vesperuginis has a broad host species and geographical distribution.
Output: Babesia vesperuginis in insectivorous bats from China
Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.
Output: ASBMT COMMITTEE REPORT Preparing for the Unthinkable: Emergency Preparedness for the Hematopoietic Cell Transplant Program
Recent outbreaks of porcine epidemic diarrhea virus (PEDV) have caused widespread concern. The identification of proteins associated with PEDV infection might provide insight into PEDV pathogenesis and facilitate the development of novel antiviral strategies. We analyzed the differential protein profile of PEDV-infected Vero E6 cells using mass spectrometry and an isobaric tag for relative and absolute quantification. A total of 126 proteins were identified that were differentially expressed between the PEDV-infected and mock-infected groups (P < 0.05, quantitative ratio ≥1.2), among which the expression of 58 proteins was up-regulated and that of 68 proteins was down-regulated in the PEDV-infected Vero E6 cells, involving in integrin ␤2/␤3, cystatin-C. The Gene Ontology analysis indicated that the molecular function of the differentially expressed proteins (DEPs) was primarily related to binding and catalytic activity, and that the biological functions in which the DEPs are involved included metabolism, organismal systems, cellular processes, genetic information processing, environmental information processing, and diseases. Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor, Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin ␤2/␤3 and cystatin-C proteins, represented potential factors in PEDV infection. Our findings provide valuable insight into PEDV-Vero E6 cell interactions.
Output: Analysis of protein expression changes of the Vero E6 cells infected with classic PEDV strain CV777 by using quantitative proteomic technique
Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity. Wildlife Trade and Human Health in Lao PDR PLOS ONE |
Output: Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets